The Multi-Modal Immune Pathogenesis of Atopic Eczema

Trends in Immunology

Volumn 36, Issue 12, 2015, Pages 788-801

  Eyerich, Kilian ^a   Eyerich, Stefanie ^a   Biedermann, Tilo ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALLERGEN;

ADAPTIVE IMMUNITY; ATOPIC DERMATITIS; CHRONIC DISEASE; CHRONIC INFLAMMATION; GENETIC TRAIT; HELPER CELL; HUMAN; IMMUNE RESPONSE; IMMUNITY; IMMUNOCOMPETENT CELL; IMMUNOPATHOGENESIS; INNATE IMMUNITY; LOSS OF FUNCTION MUTATION; MICROBIAL DIVERSITY; MICROFLORA; NONHUMAN; PERSONALIZED MEDICINE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; ANIMAL; IMMUNOLOGY; SKIN;

ADAPTIVE IMMUNITY; ANIMALS; DERMATITIS, ATOPIC; HUMANS; IMMUNITY, INNATE; SKIN;

EID: 84949729540     PISSN: 14714906     EISSN: 14714981     Source Type: Journal    
DOI: 10.1016/j.it.2015.10.006     Document Type: Review

References (101)

1. Hay R.J., et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J. Invest. Dermatol. 2014, 134:1527-1534.
2. Naik S., et al. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 2015, 520:104-108.
3. Naik S., et al. Compartmentalized control of skin immunity by resident commensals. Science 2012, 337:1115-1119.
4. Bieber T. Atopic dermatitis. N. Engl. J. Med. 2008, 358:1483-1494.
5. Bieber T. Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine. Allergy 2012, 67:1475-1482.
6. Noda S., et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased T17 polarization. J. Allergy Clin. Immunol. 2015.
7. Eyerich K., Novak N. Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy 2013, 68:974-982.
8. Palmer C.N., et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 2006, 38:441-446.
9. Irvine A.D., et al. Filaggrin mutations associated with skin and allergic diseases. N. Engl. J. Med. 2011, 365:1315-1327.
10. Weidinger S., et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J. Allergy Clin. Immunol. 2006, 118:214-219.
11. Ried J.S., et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat. Genet. 2015, Published online October 19, 2015. 10.1038/ng.3424.
12. Schmitt J., et al. Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. J. Allergy Clin. Immunol. 2015, Published online August 4, 2015. 10.1016/j.jaci.2015.06.029.
13. Henseler T., Christophers E. Disease concomitance in psoriasis. J. Am. Acad. Dermatol. 1995, 32:982-986.
14. Paternoster L., et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat. Genet. 2012, 44:187-192.
15. Esparza-Gordillo J., et al. A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis. J. Allergy Clin. Immunol. 2013, 132:371-377.
16. Quaranta M., et al. Intra-individual genome expression analysis reveals a specific molecular signature of psoriasis and eczema. Sci. Transl. Med. 2014, 6:244ra90.
17. Eckburg P.B., et al. Diversity of the human intestinal microbial flora. Science 2005, 308:1635-1638.
18. Turnbaugh P.J., et al. A core gut microbiome in obese and lean twins. Nature 2009, 457:480-484.
19. Gao Z., et al. Molecular analysis of human forearm superficial skin bacterial biota. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:2927-2932.
20. Fierer N., et al. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:17994-17999.
21. Grice E.A., et al. Topographical and temporal diversity of the human skin microbiome. Science 2009, 324:1190-1192.
22. Costello E.K., et al. Bacterial community variation in human body habitats across space and time. Science 2009, 326:1694-1697.
23. Kong H.H., et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome. Res. 2012, 22:850-859.
24. Kobayashi T., et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity 2015, 42:756-766.
25. Hill D.A., et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat. Med. 2012, 18:538-546.
26. Spencer S.P., et al. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science 2014, 343:432-437.
27. + T cells. Science 2015, 349:989-993.
28. Gueniche A., et al. Effects of nonpathogenic gram-negative bacterium Vitreoscilla filiformis lysate on atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled clinical study. Br. J. Dermatol. 2008, 159:1357-1363.
29. Volz T., et al. Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells. J. Invest. Dermatol. 2014, 134:96-104.
30. van Nood E., et al. Duodenal infusion of feces for recurrent Clostridium difficile. N. Engl. J. Med. 2013, 368:2145.
31. Schroder J.M. Antimicrobial peptides in healthy skin and atopic dermatitis. Allergol. Int. 2011, 60:17-24.
32. Biedermann T. Dissecting the role of infections in atopic dermatitis. Acta Derm. Venereol. 2006, 86:99-109.
33. Ong P.Y., et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 2002, 347:1151-1160.
34. Eyerich S., et al. Mutual antagonism of T cells causing psoriasis and atopic eczema. N. Engl. J. Med. 2011, 365:231-238.
35. Quaranta M., et al. Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema. Sci. Transl. Med. 2014, 6:244ra290.
36. Guttman-Yassky E., et al. Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J. Immunol. 2008, 181:7420-7427.
37. Guttman-Yassky E., et al. Contrasting pathogenesis of atopic dermatitis and psoriasis Part II. Immune cell subsets and therapeutic concepts. J. Allergy Clin. Immunol. 2011, 127:1420-1432.
38. Ghoreschi K., et al. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat. Med. 2003, 9:40-46.
39. Guenova E., et al. IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells. Proc. Natl. Acad. Sci. U.S.A. 2015, 112:2163-2168.
40. Howell M.D., et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 2006, 24:341-348.
41. Howell M.D., et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J. Allergy Clin. Immunol. 2009, 124(Suppl. 2):R7-R12.
42. Spits H., et al. Innate lymphoid cells - a proposal for uniform nomenclature. Nat. Rev. Immunol. 2013, 13:145-149.
43. Salimi M., et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J. Exp. Med. 2013, 210:2939-2950.
44. Roediger B., et al. Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells. Nat. Immunol. 2013, 14:564-573.
45. Soumelis V., et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 2002, 3:673-680.
46. Zheng T., et al. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J. Invest. Dermatol. 2009, 129:742-751.
47. Gold M.J., et al. Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH2-inducing allergen exposures. J. Allergy Clin. Immunol. 2014, 133:1142-1148.
48. Monticelli L.A., et al. IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc. Natl. Acad. Sci. U.S.A. 2015, 112:10762-10767.
49. Eyerich K., et al. IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response. J. Allergy Clin. Immunol. 2009, 123:59-66.e4.
50. Mempel M., et al. Toll-like receptor expression in human keratinocytes: nuclear factor kappaB controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but not toll-like receptor 4 or platelet activating factor receptor dependent. J. Invest. Dermatol. 2003, 121:1389-1396.
51. Lai Y., Gallo R.L. Toll-like receptors in skin infections and inflammatory diseases. Infect. Disord. Drug Targets 2008, 8:144-155.
52. Kang J.Y., et al. Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 2009, 31:873-884.
53. Skabytska Y., et al. Cutaneous innate immune sensing of Toll-like receptor 2-6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells. Immunity 2014, 41:762-775.
54. Novak N., et al. FcepsilonRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J. Allergy Clin. Immunol. 2004, 113:949-957.
55. Kaesler S., et al. Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10. J. Allergy Clin. Immunol. 2014, 134:92-99.
56. Biedermann T., et al. IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice. Nat. Immunol. 2001, 2:1054-1060.
57. Yao Y., et al. Interleukin (IL)-4 inhibits IL-10 to promote IL-12 production by dendritic cells. J. Exp. Med. 2005, 201:1899-1903.
58. Werfel T., et al. Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LEN. Allergy 2007, 62:723-728.
59. Werfel T., et al. Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber. J. Allergy Clin. Immunol. 2015, 136:96-103.e9.
60. Eyerich K., et al. Pollen grains induce a rapid and biphasic eczematous immune response in atopic eczema patients. Int. Arch. Allergy Immunol. 2008, 145:213-223.
61. Darsow U., et al. The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study. Allergy 2004, 59:1318-1325.
62. Scheurer S., et al. What makes an allergen?. Clin. Exp. Allergy 2015, 45:1150-1161.
63. Martin S.F. Immunological mechanisms in allergic contact dermatitis. Curr. Opin. Allergy Clin. Immunol. 2015, 15:124-130.
64. Traidl-Hoffmann C., et al. Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J. Exp. Med. 2005, 201:627-636.
65. Gilles S., Traidl-Hoffmann C. The environment-pathogen-host axis in communicable and non-communicable diseases: recent advances in experimental and clinical research. J. Dtsch. Dermatol. Ges. 2014, 12:395-399.
66. Macias E.S., et al. Superantigens in dermatology. J. Am. Acad. Dermatol. 2011, 64:455-472.
67. Niebuhr M., et al. Staphylococcal exotoxins are strong inducers of IL-22: a potential role in atopic dermatitis. J. Allergy Clin. Immunol. 2010, 126:1176-1183.e4.
68. Quaranta M., et al. Allergic contact dermatitis in psoriasis patients: typical, delayed, and non-interacting. PLoS One 2014, 9:e101814.
69. Gittler J.K., et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J. Allergy Clin. Immunol. 2012.
70. Balaji H., et al. Malassezia sympodialis thioredoxin-specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis. J. Allergy Clin. Immunol. 2011, 128:92-99.e4.
71. Cipriani F., et al. Autoimmunity in atopic dermatitis: biomarker or simply epiphenomenon?. J. Dermatol. 2014, 41:569-576.
72. Tang T.S., et al. Does 'autoreactivity' play a role in atopic dermatitis?. J. Allergy Clin. Immunol. 2012, 129:1209-1215.e2.
73. Hradetzky S., et al. Differential cytokine induction by the human skin-associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control subjects. J. Allergy Clin. Immunol. 2015, 135:1378-1380.
74. Hradetzky S., et al. Cytokine effects induced by the human autoallergen alpha-NAC. J. Invest. Dermatol. 2014, 134:1570-1578.
75. Du Toit G., et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N. Engl. J. Med. 2015, 372:803-813.
76. Lodge C.J., et al. Perinatal cat and dog exposure and the risk of asthma and allergy in the urban environment: a systematic review of longitudinal studies. Clin. Dev. Immunol. 2012, 2012:176484.
77. Lau S., et al. Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with 1 atopic parent in a randomized, placebo-controlled trial. J. Allergy Clin. Immunol. 2012, 129:1040-1047.
78. Gruber C., et al. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. J. Allergy Clin. Immunol. 2010, 126:791-797.
79. Folster-Holst R., et al. Prospective, randomized controlled trial on Lactobacillus rhamnosus in infants with moderate to severe atopic dermatitis. Br. J. Dermatol. 2006, 155:1256-1261.
80. Gruber C., et al. Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment of atopic dermatitis in infancy. Allergy 2007, 62:1270-1276.
81. Bae J.M., et al. Efficacy of allergen-specific immunotherapy for atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials. J. Allergy Clin. Immunol. 2013, 132:110-117.
82. Novak N., et al. Efficacy and safety of subcutaneous allergen-specific immunotherapy with depigmented polymerized mite extract in atopic dermatitis. J. Allergy Clin. Immunol. 2012, 130:925-931.e4.
83. Werfel T., Biedermann T. Current novel approaches in systemic therapy of atopic dermatitis: specific inhibition of cutaneous Th2 polarized inflammation and itch. Curr. Opin. Allergy Clin. Immunol. 2015, 15:446-452.
84. Navarini A.A., et al. Interrupting IL-6-receptor signaling improves atopic dermatitis but associates with bacterial superinfection. J. Allergy Clin. Immunol. 2011, 128:1128-1130.
85. Puya R., et al. Treatment of severe refractory adult atopic dermatitis with ustekinumab. Int. J. Dermatol. 2012, 51:115-116.
86. Samorano L.P., et al. Inadequate response to ustekinumab in atopic dermatitis - a report of two patients. J. Eur. Acad. Dermatol. Venereol. 2014, Published online December 16, 2014. 10.1111/jdv.12918.
87. Leckie M.J., et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000, 356:2144-2148.
88. Ortega H.G., et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N. Engl. J. Med. 2014, 371:1198-1207.
89. Pavord I.D., et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012, 380:651-659.
90. Wollenberg A., Bieber T. Proactive therapy of atopic dermatitis - an emerging concept. Allergy 2009, 64:276-278.
91. Hirota T., et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat. Genet. 2012, 44:1222-1226.
92. Ellinghaus D., et al. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat. Genet. 2013, 45:808-812.
93. Beck L.A., et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N. Engl. J. Med. 2014, 371:130-139.
94. Oldhoff J.M., et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 2005, 60:693-696.
95. Heil P.M., et al. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course - a randomized, placebo-controlled and double blind pilot study. J. Dtsch. Dermatol. Ges. 2010, 8:990-998.
96. Sheinkopf L.E., et al. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy Asthma Proc. 2008, 29:530-537.
97. Simon D., et al. Anti-CD20 (rituximab) treatment improves atopic eczema. J. Allergy Clin. Immunol. 2008, 121:122-128.
98. Sediva A., et al. Anti-CD20 (rituximab) treatment for atopic eczema. J. Allergy Clin. Immunol. 2008, 121:1515-1516.
99. Buka R.L., et al. Etanercept is minimally effective in 2 children with atopic dermatitis. J. Am. Acad. Dermatol. 2005, 53:358-359.
100. Hanifin J.M., et al. Recombinant interferon gamma therapy for atopic dermatitis. J. Am. Acad. Dermatol. 1993, 28:189-197.
101. Baurecht H., et al. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. Am. J. Hum. Genet. 2015, 96:104-120.