Molecular and cellular mechanisms of food allergy and food tolerance

Journal of Allergy and Clinical Immunology

Volumn 137, Issue 4, 2016, Pages 984-997

  Chinthrajah, R Sharon ^a   Hernandez, Joseph D ^a   Boyd, Scott D ^a   Galli, Stephen J ^a   Nadeau, Kari C ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

basophils; dendritic cells; desensitization; Food allergy; immunotherapy; mast cells; microbiome; regulatory T cells; sensitization; tolerance

Indexed keywords

FOOD ALLERGEN; FOOD ANTIGEN; PROBIOTIC AGENT; ALLERGEN; PROTEIN INTAKE;

ANAPHYLAXIS; ANTIGEN PRESENTATION; ANTIGEN SPECIFICITY; B LYMPHOCYTE; DENDRITIC CELL; DESENSITIZATION; DYSBIOSIS; FOOD ALLERGY; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOTHERAPY; INTESTINE FLORA; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTAKE; REGULATORY T LYMPHOCYTE; REVIEW; SKIN FLORA; SKIN SENSITIZATION; T LYMPHOCYTE; ATOPIC DERMATITIS; COMPLICATION; FOOD HYPERSENSITIVITY; IMMUNOLOGY; MICROBIOLOGY; PROCEDURES; RISK FACTOR;

ALLERGENS; DERMATITIS, ATOPIC; DESENSITIZATION, IMMUNOLOGIC; DIETARY PROTEINS; FOOD HYPERSENSITIVITY; GASTROINTESTINAL MICROBIOME; HUMANS; IMMUNE TOLERANCE; PROBIOTICS; RISK FACTORS;

EID: 84963969152     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2016.02.004     Document Type: Review

References (179)

1. F. Moog The lining of the small intestine Sci Am 245 1981 154 158 160, 162
2. P. Brandtzaeg Development and basic mechanisms of human gut immunity Nutr Rev 56 suppl 1998 S5 S18
3. C.A. Lozupone, J.I. Stombaugh, J.I. Gordon, J.K. Jansson, and R. Knight Diversity, stability and resilience of the human gut microbiota Nature 489 2012 220 230
4. J. Mestecky, and J.R. McGhee Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response Adv Immunol 40 1987 153 245
5. P.J. van der Heijden, W. Stok, and A.T. Bianchi Contribution of immunoglobulin-secreting cells in the murine small intestine to the total 'background' immunoglobulin production Immunology 62 1987 551 555
6. E. Untersmayr, I. Scholl, I. Swoboda, W.J. Beil, E. Forster-Waldl, F. Walter, and et al. Antacid medication inhibits digestion of dietary proteins and causes food allergy: a fish allergy model in BALB/c mice J Allergy Clin Immunol 112 2003 616 623
7. E. Untersmayr, and E. Jensen-Jarolim The role of protein digestibility and antacids on food allergy outcomes J Allergy Clin Immunol 121 2008 1301 1310
8. E. Untersmayr, N. Bakos, I. Scholl, M. Kundi, F. Roth-Walter, K. Szalai, and et al. Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients FASEB J 19 2005 656 658
9. K.S. Barone, M.R. Reilly, M.P. Flanagan, and J.G. Michael Abrogation of oral tolerance by feeding encapsulated antigen Cell Immunol 199 2000 65 72
10. M. Rescigno, M. Urbano, B. Valzasina, M. Francolini, G. Rotta, R. Bonasio, and et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria Nat Immunol 2 2001 361 367
11. S. Menard, N. Cerf-Bensussan, and M. Heyman Multiple facets of intestinal permeability and epithelial handling of dietary antigens Mucosal Immunol 3 2010 247 259
12. J.H. Niess, S. Brand, X. Gu, L. Landsman, S. Jung, B.A. McCormick, and et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance Science 307 2005 254 258
13. O. Pabst, and A.M. Mowat Oral tolerance to food protein Mucosal Immunol 5 2012 232 239
14. N.A. Mabbott, D.S. Donaldson, H. Ohno, I.R. Williams, and A. Mahajan Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium Mucosal Immunol 6 2013 666 677
15. M. Chehade, and L. Mayer Oral tolerance and its relation to food hypersensitivities J Allergy Clin Immunol 115 2005 3 13
16. R.M. Hershberg, D.H. Cho, A. Youakim, M.B. Bradley, J.S. Lee, P.E. Framson, and et al. Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells J Clin Invest 102 1998 792 803
17. C.L. Scott, A.M. Aumeunier, and A.M. Mowat Intestinal CD103+ dendritic cells: master regulators of tolerance? Trends Immunol 32 2011 412 419
18. A.J. Macpherson, and T. Uhr Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria Science 303 2004 1662 1665
19. P. Sicinski, J. Rowinski, J.B. Warchol, Z. Jarzabek, W. Gut, B. Szczygiel, and et al. Poliovirus type 1 enters the human host through intestinal M cells Gastroenterology 98 1990 56 58
20. H. Suzuki, S. Sekine, K. Kataoka, D.W. Pascual, M. Maddaloni, R. Kobayashi, and et al. Ovalbumin-protein sigma 1 M-cell targeting facilitates oral tolerance with reduction of antigen-specific CD4+ T cells Gastroenterology 135 2008 917 925
21. T.A. Kraus, J. Brimnes, C. Muong, J.H. Liu, T.M. Moran, K.A. Tappenden, and et al. Induction of mucosal tolerance in Peyer's patch-deficient, ligated small bowel loops J Clin Invest 115 2005 2234 2243
22. T.W. Spahn, A. Fontana, A.M. Faria, A.J. Slavin, H.P. Eugster, X. Zhang, and et al. Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches Eur J Immunol 31 2001 1278 1287
23. T.W. Spahn, H.L. Weiner, P.D. Rennert, N. Lugering, A. Fontana, W. Domschke, and et al. Mesenteric lymph nodes are critical for the induction of high-dose oral tolerance in the absence of Peyer's patches Eur J Immunol 32 2002 1109 1113
24. C.C. Bain, and A.M. Mowat Intestinal macrophages - specialised adaptation to a unique environment Eur J Immunol 41 2011 2494 2498
25. M. Bogunovic, F. Ginhoux, J. Helft, L. Shang, D. Hashimoto, M. Greter, and et al. Origin of the lamina propria dendritic cell network Immunity 31 2009 513 525
26. O. Schulz, E. Jaensson, E.K. Persson, X. Liu, T. Worbs, W.W. Agace, and et al. Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions J Exp Med 206 2009 3101 3114
27. A.L. Warshaw, W.A. Walker, and K.J. Isselbacher Protein uptake by the intestine: evidence for absorption of intact macromolecules Gastroenterology 66 1974 987 992
28. S. Husby, J.C. Jensenius, and S.E. Svehag Passage of undegraded dietary antigen into the blood of healthy adults. Quantification, estimation of size distribution, and relation of uptake to levels of specific antibodies Scand J Immunol 22 1985 83 92
29. W.A. Walker, and K.J. Isselbacher Uptake and transport of macromolecules by the intestine. Possible role in clinical disorders Gastroenterology 67 1974 531 550
30. A. Goubier, B. Dubois, H. Gheit, G. Joubert, F. Villard-Truc, C. Asselin-Paturel, and et al. Plasmacytoid dendritic cells mediate oral tolerance Immunity 29 2008 464 475
31. A.W. Thomson, and P.A. Knolle Antigen-presenting cell function in the tolerogenic liver environment Nat Rev Immunol 10 2010 753 766
32. H.J. Peng, M.W. Turner, and S. Strobel The generation of a 'tolerogen' after the ingestion of ovalbumin is time-dependent and unrelated to serum levels of immunoreactive antigen Clin Exp Immunol 81 1990 510 515
33. M.P. Callery, T. Kamei, and M.W. Flye The effect of portacaval shunt on delayed-hypersensitivity responses following antigen feeding J Surg Res 46 1989 391 394
34. R. Yang, Q. Liu, J.L. Grosfeld, and M.D. Pescovitz Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction J Pediatr Surg 29 1994 1145 1148
35. E. Mazzini, L. Massimiliano, G. Penna, and M. Rescigno Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1(+) macrophages to CD103(+) dendritic cells Immunity 40 2014 248 261
36. S. Milling, U. Yrlid, V. Cerovic, and G. MacPherson Subsets of migrating intestinal dendritic cells Immunol Rev 234 2010 259 267
37. T. Worbs, U. Bode, S. Yan, M.W. Hoffmann, G. Hintzen, G. Bernhardt, and et al. Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells J Exp Med 203 2006 519 527
38. M.T. Ventura, L. Polimeno, A.C. Amoruso, F. Gatti, E. Annoscia, M. Marinaro, and et al. Intestinal permeability in patients with adverse reactions to food Dig Liver Dis 38 2006 732 736
39. D.R. Clayburgh, M.W. Musch, M. Leitges, Y.X. Fu, and J.R. Turner Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo J Clin Invest 116 2006 2682 2694
40. C. Perrier, and B. Corthesy Gut permeability and food allergies Clin Exp Allergy 41 2011 20 28
41. F. Wang, W.V. Graham, Y. Wang, E.D. Witkowski, B.T. Schwarz, and J.R. Turner Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression Am J Pathol 166 2005 409 419
42. P.C. Yang, M.C. Berin, L.C. Yu, D.H. Conrad, and M.H. Perdue Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (FcepsilonRII) J Clin Invest 106 2000 879 886
43. L.C. Yu, P.C. Yang, M.C. Berin, V. Di Leo, D.H. Conrad, D.M. McKay, and et al. Enhanced transepithelial antigen transport in intestine of allergic mice is mediated by IgE/CD23 and regulated by interleukin-4 Gastroenterology 121 2001 370 381
44. S.J. Chambers, E. Bertelli, M.S. Winterbone, M. Regoli, A.L. Man, and C. Nicoletti Adoptive transfer of dendritic cells from allergic mice induces specific immunoglobulin E antibody in naive recipients in absence of antigen challenge without altering the T helper 1/T helper 2 balance Immunology 112 2004 72 79
45. H.A. Brough, A. Simpson, K. Makinson, J. Hankinson, S. Brown, A. Douiri, and et al. Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations J Allergy Clin Immunol 134 2014 867 875.e1
46. S. Makinen-Kiljunen, and H. Mussalo-Rauhamaa Casein, an important house dust allergen Allergy 57 2002 1084 1085
47. P. Di Meglio, K. Perera Gayathri, and O. Nestle Frank The multitasking organ: recent insights into skin immune function Immunity 35 2011 857 869
48. E. Klechevsky, R. Morita, M. Liu, Y. Cao, S. Coquery, L. Thompson-Snipes, and et al. Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells Immunity 29 2008 497 510
49. G. Du Toit, G. Roberts, P.H. Sayre, M. Plaut, H.T. Bahnson, H. Mitchell, and et al. Identifying infants at high risk of peanut allergy: the Learning Early About Peanut Allergy (LEAP) screening study J Allergy Clin Immunol 131 2013 135-43.e1-12
50. K.S. Kim, S.W. Hong, D. Han, J. Yi, J. Jung, B.G. Yang, and et al. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine Science 351 2016 858 863
51. B. Swiatczak, and M. Rescigno How the interplay between antigen presenting cells and microbiota tunes host immune responses in the gut Semin Immunol 24 2012 43 49
52. J.L. Coombes, K.R. Siddiqui, C.V. Arancibia-Carcamo, J. Hall, C.M. Sun, Y. Belkaid, and et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism J Exp Med 204 2007 1757 1764
53. H. Paidassi, M. Acharya, A. Zhang, S. Mukhopadhyay, M. Kwon, C. Chow, and et al. Preferential expression of integrin alphavbeta8 promotes generation of regulatory T cells by mouse CD103+ dendritic cells Gastroenterology 141 2011 1813 1820
54. J.J. Worthington, B.I. Czajkowska, A.C. Melton, and M.A. Travis Intestinal dendritic cells specialize to activate transforming growth factor-beta and induce Foxp3+ regulatory T cells via integrin alphavbeta8 Gastroenterology 141 2011 1802 1812
55. G. Matteoli, E. Mazzini, I.D. Iliev, E. Mileti, F. Fallarino, P. Puccetti, and et al. Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction Gut 59 2010 595 604
56. R. Molenaar, M. Greuter, A.P. van der Marel, R. Roozendaal, S.F. Martin, F. Edele, and et al. Lymph node stromal cells support dendritic cell-induced gut-homing of T cells J Immunol 183 2009 6395 6402
57. E. Jaensson, H. Uronen-Hansson, O. Pabst, B. Eksteen, J. Tian, J.L. Coombes, and et al. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans J Exp Med 205 2008 2139 2149
58. S.I. Hammerschmidt, M. Ahrendt, U. Bode, B. Wahl, E. Kremmer, R. Forster, and et al. Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo J Exp Med 205 2008 2483 2490
59. J.R. Mora, M. Iwata, B. Eksteen, S.Y. Song, T. Junt, B. Senman, and et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells Science 314 2006 1157 1160
60. T.R. Torgerson, A. Linane, N. Moes, S. Anover, V. Mateo, F. Rieux-Laucat, and et al. Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene Gastroenterology 132 2007 1705 1717
61. B. Dubois, L. Chapat, A. Goubier, M. Papiernik, J.F. Nicolas, and D. Kaiserlian Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation Blood 102 2003 3295 3301
62. U. Hadis, B. Wahl, O. Schulz, M. Hardtke-Wolenski, A. Schippers, N. Wagner, and et al. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria Immunity 34 2011 237 246
63. S. Sakaguchi, T. Yamaguchi, T. Nomura, and M. Ono Regulatory T cells and immune tolerance Cell 133 2008 775 787
64. S. Sakaguchi, D.A. Vignali, A.Y. Rudensky, R.E. Niec, and H. Waldmann The plasticity and stability of regulatory T cells Nat Rev Immunol 13 2013 461 467
65. C.L. Maynard, L.E. Harrington, K.M. Janowski, J.R. Oliver, C.L. Zindl, A.Y. Rudensky, and et al. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10 Nat Immunol 8 2007 931 941
66. M. Battaglia, C. Gianfrani, S. Gregori, and M.G. Roncarolo IL-10-producing T regulatory type 1 cells and oral tolerance Ann N Y Acad Sci 1029 2004 142 153
67. M.A. Curotto de Lafaille, N. Kutchukhidze, S. Shen, Y. Ding, H. Yee, and J.J. Lafaille Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation Immunity 29 2008 114 126
68. B. Cassani, E.J. Villablanca, F.J. Quintana, P.E. Love, A. Lacy-Hulbert, W.S. Blaner, and et al. Gut-tropic T cells that express integrin alpha4beta7 and CCR9 are required for induction of oral immune tolerance in mice Gastroenterology 141 2011 2109 2118
69. M. Tsuji, N. Komatsu, S. Kawamoto, K. Suzuki, O. Kanagawa, T. Honjo, and et al. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches Science 323 2009 1488 1492
70. H. Hammad, and B.N. Lambrecht Barrier epithelial cells and the control of type 2 immunity Immunity 43 2015 29 40
71. D.K. Chu, A. Llop-Guevara, T.D. Walker, K. Flader, S. Goncharova, J.E. Boudreau, and et al. IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization J Allergy Clin Immunol 131 2013 187-200.e1-8
72. A.B. Blazquez, and M.C. Berin Gastrointestinal dendritic cells promote Th2 skewing via OX40L J Immunol 180 2008 4441 4450
73. B.N. Lambrecht, and H. Hammad Allergens and the airway epithelium response: gateway to allergic sensitization J Allergy Clin Immunol 134 2014 499 507
74. C.A. Herbert, C.M. King, P.C. Ring, S.T. Holgate, G.A. Stewart, P.J. Thompson, and et al. Augmentation of permeability in the bronchial epithelium by the house dust mite allergen Der p1 Am J Respir Cell Mol Biol 12 1995 369 378
75. F. Shakib, O. Schulz, and H. Sewell A mite subversive: cleavage of CD23 and CD25 by Der p 1 enhances allergenicity Immunol Today 19 1998 313 316
76. S. Jyonouchi, V. Abraham, J.S. Orange, J.M. Spergel, L. Gober, E. Dudek, and et al. Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin J Allergy Clin Immunol 128 2011 102 109.e13
77. W.G. Shreffler, R.R. Castro, Z.Y. Kucuk, Z. Charlop-Powers, G. Grishina, S. Yoo, and et al. The major glycoprotein allergen from Arachis hypogaea, Ara h 1, is a ligand of dendritic cell-specific ICAM-grabbing nonintegrin and acts as a Th2 adjuvant in vitro J Immunol 177 2006 3677 3685
78. R.D. Huby, R.J. Dearman, and I. Kimber Why are some proteins allergens? Toxicol Sci 55 2000 235 246
79. A.M. Smith, and M.D. Chapman Reduction in IgE binding to allergen variants generated by site-directed mutagenesis: contribution of disulfide bonds to the antigenic structure of the major house dust mite allergen Der p 2 Mol Immunol 33 1996 399 405
80. S. Olsson, M. van Hage-Hamsten, and P. Whitley Contribution of disulphide bonds to antigenicity of Lep d 2, the major allergen of the dust mite Lepidoglyphus destructor Mol Immunol 35 1998 1017 1023
81. J.D. Astwood, J.N. Leach, and R.L. Fuchs Stability of food allergens to digestion in vitro Nat Biotechnol 14 1996 1269 1273
82. A. Nowak-Wegrzyn, and A. Fiocchi Rare, medium, or well done? The effect of heating and food matrix on food protein allergenicity Curr Opin Allergy Clin Immunol 9 2009 234 237
83. A. Nowak-Wegrzyn, K.A. Bloom, S.H. Sicherer, W.G. Shreffler, S. Noone, N. Wanich, and et al. Tolerance to extensively heated milk in children with cow's milk allergy J Allergy Clin Immunol 122 2008 342 347 347.e1-2
84. J.S. Kim, A. Nowak-Wȩgrzyn, S.H. Sicherer, S. Noone, E.L. Moshier, and H.A. Sampson Dietary baked milk accelerates the resolution of cow's milk allergy in children J Allergy Clin Immunol 128 2011 125 131.e2
85. S.A. Leonard, H.A. Sampson, S.H. Sicherer, S. Noone, E.L. Moshier, J. Godbold, and et al. Dietary baked egg accelerates resolution of egg allergy in children J Allergy Clin Immunol 130 2012 473 480.e1
86. C.M. Webber, and R.W. England Oral allergy syndrome: a clinical, diagnostic, and therapeutic challenge Ann Allergy Asthma Immunol 104 2010 101 108
87. A.E. Moghaddam, W.R. Hillson, M. Noti, K.H. Gartlan, S. Johnson, B. Thomas, and et al. Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice J Allergy Clin Immunol 134 2014 1453 1456
88. S.J. Maleki, S.-Y. Chung, E.T. Champagne, and J.-P. Raufman The effects of roasting on the allergenic properties of peanut proteins J Allergy Clin Immunol 106 2000 763 768
89. C.N. Palmer, A.D. Irvine, A. Terron-Kwiatkowski, Y. Zhao, H. Liao, S.P. Lee, and et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis Nat Genet 38 2006 441 446
90. I. Marenholz, R. Nickel, F. Rüschendorf, F. Schulz, J. Esparza-Gordillo, T. Kerscher, and et al. Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march J Allergy Clin Immunol 118 2006 866 871
91. D. Venkataraman, N. Soto-Ramírez, R.J. Kurukulaaratchy, J.W. Holloway, W. Karmaus, S.L. Ewart, and et al. Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence J Allergy Clin Immunol 134 2014 876 882.e4
92. T. Kusunoki, I. Okafuji, T. Yoshioka, M. Saito, R. Nishikomori, T. Heike, and et al. SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis J Allergy Clin Immunol 115 2005 636 638
93. H.A. Brough, A.H. Liu, S. Sicherer, K. Makinson, A. Douiri, S.J. Brown, and et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy J Allergy Clin Immunol 135 2015 164 170
94. E.L. Simpson, J.R. Chalmers, J.M. Hanifin, K.S. Thomas, M.J. Cork, W.H.I. McLean, and et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention J Allergy Clin Immunol 134 2014 818 823
95. K. Horimukai, K. Morita, M. Narita, M. Kondo, H. Kitazawa, M. Nozaki, and et al. Application of moisturizer to neonates prevents development of atopic dermatitis J Allergy Clin Immunol 134 2014 824 830.e6
96. L. Tordesillas, R. Goswami, S. Benede, G. Grishina, D. Dunkin, K.M. Jarvinen, and et al. Skin exposure promotes a Th2-dependent sensitization to peanut allergens J Clin Invest 124 2014 4965 4975
97. T. Yatsunenko, F.E. Rey, M.J. Manary, I. Trehan, M.G. Dominguez-Bello, M. Contreras, and et al. Human gut microbiome viewed across age and geography Nature 486 2012 222 227
98. R.I. Mackie, A. Sghir, and H.R. Gaskins Developmental microbial ecology of the neonatal gastrointestinal tract Am J Clin Nutr 69 1999 1035S 1045S
99. C. Palmer, E.M. Bik, D.B. DiGiulio, D.A. Relman, and P.O. Brown Development of the human infant intestinal microbiota PLoS Biol 5 2007 e177
100. S.L. Schnorr, M. Candela, S. Rampelli, M. Centanni, C. Consolandi, G. Basaglia, and et al. Gut microbiome of the Hadza hunter-gatherers Nat Commun 5 2014 3654
101. M.J. Ege, M. Mayer, A.C. Normand, J. Genuneit, W.O. Cookson, C. Braun-Fahrlander, and et al. Exposure to environmental microorganisms and childhood asthma N Engl J Med 364 2011 701 709
102. L.A. David, A. Weil, E.T. Ryan, S.B. Calderwood, J.B. Harris, F. Chowdhury, and et al. Gut microbial succession follows acute secretory diarrhea in humans MBio 6 2015 e00381 e003815
103. G.D. Wu, J. Chen, C. Hoffmann, K. Bittinger, Y.Y. Chen, S.A. Keilbaugh, and et al. Linking long-term dietary patterns with gut microbial enterotypes Science 334 2011 105 108
104. A.T. Stefka, T. Feehley, P. Tripathi, J. Qiu, K. McCoy, S.K. Mazmanian, and et al. Commensal bacteria protect against food allergen sensitization Proc Natl Acad Sci U S A 111 2014 13145 13150
105. A.J. Macpherson, Y. Koller, and K.D. McCoy The bilateral responsiveness between intestinal microbes and IgA Trends Immunol 36 2015 460 470
106. K. Suzuki, B. Meek, Y. Doi, M. Muramatsu, T. Chiba, T. Honjo, and et al. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut Proc Natl Acad Sci U S A 101 2004 1981 1986
107. K. Atarashi, T. Tanoue, K. Oshima, W. Suda, Y. Nagano, H. Nishikawa, and et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota Nature 500 2013 232 236
108. K. Atarashi, T. Tanoue, T. Shima, A. Imaoka, T. Kuwahara, Y. Momose, and et al. Induction of colonic regulatory T cells by indigenous Clostridium species Science 331 2011 337 341
109. R. Berni Canani, J.A. Gilbert, and C.R. Nagler The role of the commensal microbiota in the regulation of tolerance to dietary allergens Curr Opin Allergy Clin Immunol 15 2015 243 249
110. S. Cao, T.J. Feehley, and C.R. Nagler The role of commensal bacteria in the regulation of sensitization to food allergens FEBS Lett 588 2014 4258 4266
111. A.N. Thorburn, L. Macia, and C.R. Mackay Diet, metabolites, and "western-lifestyle" inflammatory diseases Immunity 40 2014 833 842
112. M. Vital, A.C. Howe, and J.M. Tiedje Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data MBio 5 2014 e00889
113. L. Macia, J. Tan, A.T. Vieira, K. Leach, D. Stanley, S. Luong, and et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome Nat Commun 6 2015 6734
114. N. Singh, A. Gurav, S. Sivaprakasam, E. Brady, R. Padia, H. Shi, and et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis Immunity 40 2014 128 139
115. N. Arpaia, C. Campbell, X. Fan, S. Dikiy, J. van der Veeken, P. deRoos, and et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation Nature 504 2013 451 455
116. Y. Furusawa, Y. Obata, S. Fukuda, T.A. Endo, G. Nakato, D. Takahashi, and et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells Nature 504 2013 446 450
117. P.M. Smith, M.R. Howitt, N. Panikov, M. Michaud, C.A. Gallini, Y.M. Bohlooly, and et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis Science 341 2013 569 573
118. M.B. Azad, T. Konya, D.S. Guttman, C.J. Field, M.R. Sears, K.T. HayGlass, and et al. Infant gut microbiota and food sensitization: associations in the first year of life Clin Exp Allergy 45 2015 632 643
119. L. Dethlefsen, S. Huse, M.L. Sogin, and D.A. Relman The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing PLoS Biol 6 2008 e280
120. H.E. Jakobsson, C. Jernberg, A.F. Andersson, M. Sjolund-Karlsson, J.K. Jansson, and L. Engstrand Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome PLoS One 5 2010 e9836
121. L.M. Cox, S. Yamanishi, J. Sohn, A.V. Alekseyenko, J.M. Leung, I. Cho, and et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences Cell 158 2014 705 721
122. J. Metsala, A. Lundqvist, L.J. Virta, M. Kaila, M. Gissler, and S.M. Virtanen Mother's and offspring's use of antibiotics and infant allergy to cow's milk Epidemiology 24 2013 303 309
123. J.H. Savage, E.C. Matsui, R.A. Wood, and C.A. Keet Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization J Allergy Clin Immunol 130 2012 453 460.e7
124. R. Berni Canani, N. Sangwan, A.T. Stefka, R. Nocerino, L. Paparo, R. Aitoro, and et al. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants ISME J 10 2016 742 750
125. Z. Ling, Z. Li, X. Liu, Y. Cheng, Y. Luo, X. Tong, and et al. Altered fecal microbiota composition associated with food allergy in infants Appl Environ Microbiol 80 2014 2546 2554
126. T. Kobayashi, M. Glatz, K. Horiuchi, H. Kawasaki, H. Akiyama, D.H. Kaplan, and et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis Immunity 42 2015 756 766
127. M.R. Williams, and R.L. Gallo The role of the skin microbiome in atopic dermatitis Curr Allergy Asthma Rep 15 2015 65
128. E. Forbes-Blom, M. Camberis, M. Prout, S.C. Tang, and G. Le Gros Staphylococcal-derived superantigen enhances peanut induced Th2 responses in the skin Clin Exp Allergy 42 2012 305 314
129. K. Ganeshan, C.V. Neilsen, A. Hadsaitong, R.P. Schleimer, X. Luo, and P.J. Bryce Impairing oral tolerance promotes allergy and anaphylaxis: a new murine food allergy model J Allergy Clin Immunol 123 2009 231 238.e4
130. N. Elazab, A. Mendy, J. Gasana, E.R. Vieira, A. Quizon, and E. Forno Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials Pediatrics 132 2013 e666 e676
131. R. Berni Canani, R. Nocerino, G. Terrin, A. Coruzzo, L. Cosenza, L. Leone, and et al. Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: a randomized trial J Allergy Clin Immunol 129 2012 580 582 582.e1-5
132. R. Berni Canani, R. Nocerino, G. Terrin, T. Frediani, S. Lucarelli, L. Cosenza, and et al. Formula selection for management of children with cow's milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study J Pediatr 163 2013 771 777.e1
133. J. Hol, E.H. van Leer, B.E. Elink Schuurman, L.F. de Ruiter, J.N. Samsom, W. Hop, and et al. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial J Allergy Clin Immunol 121 2008 1448 1454
134. M.L. Tang, A.L. Ponsonby, F. Orsini, D. Tey, M. Robinson, E.L. Su, and et al. Administration of a probiotic with peanut oral immunotherapy: a randomized trial J Allergy Clin Immunol 135 2015 737 744.e8
135. A. Schofield A case of egg poisoning Lancet 171 1908 716
136. H.S. Nelson, J. Lahr, R. Rule, A. Bock, and D. Leung Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract J Allergy Clin Immunol 99 1997 744 751
137. C. Dupont, N. Kalach, P. Soulaines, S. Legoué-Morillon, H. Piloquet, and P.-H. Benhamou Cow's milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity J Allergy Clin Immunol 125 2010 1165 1167
138. Dupont C. Peanut epicutaneous immunotherapy (EPIT) in peanut-allergic children: 18 months treatment in the ARACHILD Study. In: 2014 American Academy of Allergy, Asthma & Immunology Annual Meeting, San Diego, CA; 2014.
139. D. De Boissieu, and C. Dupont Sublingual immunotherapy for cow's milk protein allergy: a preliminary report Allergy 61 2006 1238 1239
140. E.H. Kim, J.A. Bird, M. Kulis, S. Laubach, L. Pons, W. Shreffler, and et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization J Allergy Clin Immunol 127 2011 640 646.e1
141. D.M. Fleischer, A.W. Burks, B.P. Vickery, A.M. Scurlock, R.A. Wood, S.M. Jones, and et al. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial J Allergy Clin Immunol 131 2013 119-27.e1-7
142. P. Bégin, L.C. Winterroth, T. Dominguez, S.P. Wilson, L. Bacal, A. Mehrotra, and et al. Safety and feasibility of oral immunotherapy to multiple allergens for food allergy Allergy Asthma Clin Immunol 10 2014 1
143. C.A. Keet, P.A. Frischmeyer-Guerrerio, A. Thyagarajan, J.T. Schroeder, R.G. Hamilton, S. Boden, and et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy J Allergy Clin Immunol 129 2012 448 455 455.e1-5
144. E. Enrique, F. Pineda, T. Malek, J. Bartra, M. Basagaña, R. Tella, and et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract J Allergy Clin Immunol 116 2005 1073 1079
145. K.C. Nadeau, L.C. Schneider, L. Hoyte, I. Borras, and D.T. Umetsu Rapid oral desensitization in combination with omalizumab therapy in patients with cow's milk allergy J Allergy Clin Immunol 127 2011 1622 1624
146. L.C. Schneider, R. Rachid, J. LeBovidge, E. Blood, M. Mittal, and D.T. Umetsu A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients J Allergy Clin Immunol 132 2013 1368 1374
147. P. Begin, T. Dominguez, S.P. Wilson, L. Bacal, A. Mehrotra, B. Kausch, and et al. Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using omalizumab Allergy Asthma Clin Immunol 10 2014 7
148. R.A. Wood, J.S. Kim, R. Lindblad, K. Nadeau, A.K. Henning, P. Dawson, and et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy J Allergy Clin Immunol 137 2016 1103 1110
149. P. Begin, R.S. Chinthrajah, and K.C. Nadeau Oral immunotherapy for the treatment of food allergy Hum Vaccin Immunother 10 2014 2295 2302
150. M. Akdis, and C.A. Akdis Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens J Allergy Clin Immunol 133 2014 621 631
151. A. Syed, M.A. Garcia, S.C. Lyu, R. Bucayu, A. Kohli, S. Ishida, and et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3) J Allergy Clin Immunol 133 2014 500 510
152. A.W. Burks, S.M. Jones, R.A. Wood, D.M. Fleischer, S.H. Sicherer, R.W. Lindblad, and et al. Oral immunotherapy for treatment of egg allergy in children N Engl J Med 367 2012 233 243
153. S.M. Jones, L. Pons, J.L. Roberts, A.M. Scurlock, T.T. Perry, M. Kulis, and et al. Clinical efficacy and immune regulation with peanut oral immunotherapy J Allergy Clin Immunol 124 2009 292 300 300.e1-97
154. M.V. Khodoun, Z.Y. Kucuk, R.T. Strait, D. Krishnamurthy, K. Janek, C.D. Clay, and et al. Rapid desensitization of mice with anti-FcgammaRIIb/FcgammaRIII mAb safely prevents IgG-mediated anaphylaxis J Allergy Clin Immunol 132 2013 1375 1387
155. T. Oka, E.J. Rios, M. Tsai, J. Kalesnikoff, and S.J. Galli Rapid desensitization induces internalization of antigen-specific IgE on mouse mast cells J Allergy Clin Immunol 132 2013 922-32.e1-16
156. S.A. Leonard, G. Martos, W. Wang, A. Nowak-Wegrzyn, and M.C. Berin Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa J Allergy Clin Immunol 129 2012 1579 1587.e1
157. M. Jutel, U. Muller, M. Ericker, S. Rihs, W. Pichler, and C. Dahinden Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils Clin Exp Allergy 26 1996 1112 1118
158. B. Eberlein-Konig, S. Ullmann, P. Thomas, and B. Przybilla Tryptase and histamine release due to a sting challenge in bee venom allergic patients treated successfully or unsuccessfully with hyposensitization∗ Clin Exp Allergy 25 1995 704 712
159. H.Y. Woo, Y.S. Kim, N.I. Kang, W.C. Chung, C.H. Song, I.W. Choi, and et al. Mechanism for acute oral desensitization to antibiotics Allergy 61 2006 954 958
160. C. Bussmann, J. Xia, J.P. Allam, L. Maintz, T. Bieber, and N. Novak Early markers for protective mechanisms during rush venom immunotherapy Allergy 65 2010 1558 1565
161. J.-P. Allam, P.A. Würtzen, M. Reinartz, J. Winter, S. Vrtala, K.-W. Chen, and et al. Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-β1 and IL-10-producing properties J Allergy Clin Immunol 126 2010 638 645.e1
162. M. Lao-Araya, E. Steveling, G.W. Scadding, S.R. Durham, and M.H. Shamji Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy J Allergy Clin Immunol 134 2014 1193
163. P. Licona-Limón, L.K. Kim, N.W. Palm, and R.A. Flavell TH2, allergy and group 2 innate lymphoid cells Nat Immunol 14 2013 536 542
164. M. Salimi, J.L. Barlow, S.P. Saunders, L. Xue, D. Gutowska-Owsiak, X. Wang, and et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis J Exp Med 210 2013 2939 2950
165. T.A. Doherty, D. Scott, H.H. Walford, N. Khorram, S. Lund, R. Baum, and et al. Allergen challenge in allergic rhinitis rapidly induces increased peripheral blood type 2 innate lymphoid cells that express CD84 J Allergy Clin Immunol 133 2014 1203 1205
166. S. Yu, H.Y. Kim, Y.-J. Chang, R.H. DeKruyff, and D.T. Umetsu Innate lymphoid cells and asthma J Allergy Clin Immunol 133 2014 943 950
167. V. Dioszeghy, L. Mondoulet, V. Dhelft, M. Ligouis, E. Puteaux, P.-H. Benhamou, and et al. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice J Immunol 186 2011 5629 5637
168. L. Mondoulet, V. Dioszeghy, E. Puteaux, M. Ligouis, V. Dhelft, F. Letourneur, and et al. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice Clin Transl Allergy 2 2012 22
169. M. Akdis, J. Verhagen, A. Taylor, F. Karamloo, C. Karagiannidis, R. Crameri, and et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells J Exp Med 199 2004 1567 1575
170. P.L. Smaldini, M.L.O. Delgado, C.A. Fossati, and G.H. Docena Orally-induced intestinal CD4+ CD25+ FoxP3+ Treg controlled undesired responses towards oral antigens and effectively dampened food allergic reactions PLoS One 10 2015 e0141116
171. A. Aslam, H. Chan, D.A. Warrell, S. Misbah, and G.S. Ogg Tracking antigen-specific T-cells during clinical tolerance induction in humans PLoS One 5 2010 e11028
172. J.F. Ryan, R. Hovde, J. Glanville, S.C. Lyu, X. Ji, S. Gupta, and et al. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets Proc Natl Acad Sci U S A 2016 [Epub ahead of print]
173. B.P. Vickery, J. Lin, M. Kulis, Z. Fu, P.H. Steele, S.M. Jones, and et al. Peanut oral immunotherapy modifies IgE and IgG 4 responses to major peanut allergens J Allergy Clin Immunol 131 2013 128-34.e1-3
174. R.A. Hoh, S.A. Joshi, Y. Liu, C. Wang, K.M. Roskin, J.-Y. Lee, and et al. Single B-cell deconvolution of peanut-specific antibody responses in allergic patients J Allergy Clin Immunol 137 2016 157 167
175. A.F. Santos, L.K. James, H.T. Bahnson, M.H. Shamji, N.C. Couto-Francisco, S. Islam, and et al. IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens J Allergy Clin Immunol 135 2015 1249 1256
176. O.T. Burton, S.L. Logsdon, J.S. Zhou, J. Medina-Tamayo, A. Abdel-Gadir, M. Noval Rivas, and et al. Oral immunotherapy induces IgG antibodies that act through FcgammaRIIb to suppress IgE-mediated hypersensitivity J Allergy Clin Immunol 134 2014 1310 1317.e6
177. R.T. Strait, S.C. Morris, and F.D. Finkelman IgG-blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and Fc gamma RIIb cross-linking J Clin Invest 116 2006 833 841
178. G.N. Konstantinou, A. Nowak-Wȩgrzyn, R. Bencharitiwong, L. Bardina, S.H. Sicherer, and H.A. Sampson Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: Is there a role in tolerance induction? Pediatr Allergy Immunol 25 2014 64 70
179. W. van de Veen, B. Stanic, G. Yaman, M. Wawrzyniak, S. Söllner, D.G. Akdis, and et al. IgG 4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses J Allergy Clin Immunol 131 2013 1204 1212