Neuroimmune modulation of gut function

Handbook of Experimental Pharmacology

Volumn 239, Issue , 2017, Pages 247-267

  Shea Donohue, Terez ^a   Urban, Joseph F ^b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b BELTSVILLE HUMAN NUTRITION RESEARCH CENTER   (United States)

Author keywords

Innate lymphoid cell; Macrophage; Mast cell; Neuroimmune plasticity; Neuroimmune synapse; T cell; Vagal cholinergic reflex

Indexed keywords

ARTICLE; AUTONOMIC NERVOUS SYSTEM; CELL COMMUNICATION; GLIA CELL; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INFLAMMATION; INTESTINE FUNCTION; INTESTINE INNERVATION; INTESTINE MUCOSA; LYMPHOID CELL; MACROPHAGE; MAST CELL; NERVE CELL; NERVE CELL PLASTICITY; NONHUMAN; PERMEABILITY BARRIER; T LYMPHOCYTE; ANIMAL; GASTROINTESTINAL DISEASES; GASTROINTESTINAL TRACT; GLIA; IMMUNE SYSTEM; IMMUNOLOGICAL SYNAPSE; IMMUNOLOGY; INNERVATION; MUCOSAL IMMUNITY; PATHOPHYSIOLOGY; REFLEX; TUMOR MICROENVIRONMENT;

ANIMALS; CELLULAR MICROENVIRONMENT; ENTERIC NERVOUS SYSTEM; GASTROINTESTINAL DISEASES; GASTROINTESTINAL TRACT; HUMANS; IMMUNE SYSTEM; IMMUNITY, MUCOSAL; IMMUNOLOGICAL SYNAPSES; INFLAMMATION; MACROPHAGES; MAST CELLS; NEUROGLIA; NEUROIMMUNOMODULATION; NEURONAL PLASTICITY; REFLEX; T-LYMPHOCYTES;

EID: 85018511062     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/164_2016_109     Document Type: Article

References (128)

1. Andersson U, Tracey KJ (2012) Reflex principles of immunological homeostasis. Annu Rev Immunol 30: 313-335
2. Antalis TM, Shea-Donohue T, Vogel SN et al (2007) Mechanisms of disease: protease functions in intestinal mucosal pathobiology. Nat Clin Pract Gastroenterol Hepatol 4: 393-402
3. Artis D, Spits H (2015) The biology of innate lymphoid cells. Nature 517: 293-301
4. Assas BM, Miyan JA, Pennock JL (2014) Cross-talk between neural and immune receptors provides a potential mechanism of homeostatic regulation in the gut mucosa. Mucosal Immunol 7: 1283-1289
5. Bai A, Lu N, Guo Y et al (2009) Modulation of inflammatory response via α2-adrenoceptor blockade in acute murine colitis. Clin Exp Immunol 156: 353-362
6. Bain CC, Scott CL, Uronen-Hansson H et al (2013) Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol 6: 498-510
7. Bamias G, Nyce MR, De La Rue SA et al (2005) New concepts in the pathophysiology of inflammatory bowel disease. Ann Intern Med 143: 895-904
8. Bansal V, Ryu SY, Lopez N et al (2012) Vagal stimulation modulates inflammation through a ghrelin mediated mechanism in traumatic brain injury. Inflammation 35: 214-220
9. Bedoui S, Gebhardt T, Gasteiger G et al (2016) Parallels and differences between innate and adaptive lymphocytes. Nat Immunol 17: 490-494
10. Bettelli E, Korn T, Oukka M et al (2008) Induction and effector functions of TH17 cells. Nature 453: 1051-1057
11. Borovikova LV, Ivanova S, Zhang M et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458-462
12. Brun P, Giron MC, Qesari M et al (2013) Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 145: 1323-1333
13. Bush TG, Savidge TC, Freeman TC et al (1998) Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93: 189-201
14. Cailotto C, Gomez-Pinilla PJ, Costes LM et al (2014) Neuro-anatomical evidence indicating indirect modulation of macrophages by vagal efferents in the intestine but not in the spleen. PLoS One 9:e87785
15. Camilleri M, Acosta A (2015) Relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist. Neurogastroenterol Motil 27: 324-332
16. Camilleri M, Papathanasopoulos A, Odunsi ST (2009) Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol 6: 343-352
17. Camilleri M, Madsen K, Spiller R et al (2012) Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil 24: 503-512
18. Capoccia E, Cirillo C, Gigli S et al (2015) Enteric glia: a new player in inflammatory bowel diseases. Int J Immunopathol Pharmacol 28: 443-451
19. Cenac N, Andrews CN, Holzhausen M et al (2007) Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Investig 117: 636-647
20. Chang C-H, Pearce EL (2016a) Emerging concepts in immunotherapy-T cell metabolism as a therapeutic target. Nat Immunol 17: 364-368
21. Chang C-H, Pearce EL (2016b) Emerging concepts of T cell metabolism as a target of immunotherapy. Nat Immunol 17: 364-368
22. Cooper MD, Alder MN (2006) The evolution of adaptive immune systems. Cell 124: 815-822
23. Costantini TW, Bansal V, KrzyzaniakM et al (2010) Vagal nerve stimulation protects against burninduced intestinal injury through activation of enteric glia cells. Am J Physiol Gastrointest Liver Physiol 299:G1308-G1318
24. Costantini TW, Krzyzaniak M, Cheadle GA et al (2012) Targeting α-7 nicotinic acetylcholine receptor in the enteric nervous system: a cholinergic agonist prevents gut barrier failure after severe burn injury. Am J Pathol 181: 478-486
25. Cua DJ, Kastelein RA (2006) TGF-[beta], a "double agent" in the immune pathology war. Nat Immunol 7: 557-559
26. De Giorgio R, Giancola F, Boschetti E et al (2012) Enteric glia and neuroprotection: basic and clinical aspects. Am J Physiol Gastrointest Liver Physiol 303:G887-G893
27. de Jonge WJ (2013) The gut’s little brain in control of intestinal immunity. ISRN Gastroenterol 2013:630159
28. de Jonge WJ, Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151: 915-929
29. de Jonge WJ, van der Zanden EP, The FO et al (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6: 844-851
30. Di Giovangiulio M, Verheijden S, Bosmans G et al (2015a) The neuromodulation of the intestinal immune system and its relevance in inflammatory bowel disease. Front Immunol 6:590
31. Di Giovangiulio M, Stakenborg N, Bosmans G et al (2015b) Ghrelin receptor modulates T helper cells during intestinal inflammation. Neurogastroenterol Motil 27: 1542-1552
32. Dustin ML (2012) Signaling at neuro/immune synapses. J Clin Investig 122: 1149-1155
33. Eskandari MK, Kalff JC, Billiar TR et al (1999) LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity. Am J Physiol Gastrointest Liver Physiol 277: G478-G486
34. Fasano A, Shea-Donohue T (2005) Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2: 416-422
35. Fort MM, Cheung J, Yen D et al (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15: 985-995
36. Franco R, Pacheco R, Lluis C et al (2007) The emergence of neurotransmitters as immune modulators. Trends Immunol 28: 400-407
37. Fujihashi K, Kiyono H (2009) Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol 30: 334-343
38. Fujino S, Andoh A, Bamba S et al (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52: 65-70
39. Gerbe F, Sidot E, Smyth DJ et al (2016) Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529: 226-230
40. Gourbeyre P, Berri M, Lippi Y et al (2015) Pattern recognition receptors in the gut: analysis of their expression along the intestinal tract and the crypt/villus axis. Physiol Rep 3:e12225
41. Gren ST, Grip O (2016) Role of monocytes and intestinal macrophages in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 22: 1992-1998
42. Hadis U, Wahl B, Schulz O et al (2011) Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 34: 237-246
43. Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6: 1123-1132
44. Hegazy AN, Powrie F (2015) Microbiota RORgulates intestinal suppressor T cells. Science 349: 929-930
45. Hori M, Nobe H, Horiguchi K et al (2008) MCP-1 targeting inhibits muscularis macrophage recruitment and intestinal smooth muscle dysfunction in colonic inflammation. Am J Physiol Cell Physiol 294:C391-C401
46. Iwasaki A, Medzhitov R (2015) Control of adaptive immunity by the innate immune system. Nat Immunol 16: 343-353
47. Jung M-Y, Smrž D, Desai A et al (2013) IL-33 induces a hypo-responsive phenotype in human and mouse mast cells. J Immunol 190: 531-538
48. Kleinschek MA, Owyang AM, Joyce-Shaikh B, et al. (2007) IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med 204: 161-170
49. Klose CSN, Artis D (2016) Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat Immunol 17: 765-774
50. Lapointe TK, Basso L, Iftinca MC et al (2015) TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis. Am J Physiol Gastrointest Liver Physiol 309:G87-G99
51. Lee SH, Starkey PM, Gordon S (1985) Quantitative analysis of total macrophage content in adultmouse tissues. Immunochemical studies with monoclonal antibody F4/80. J Exp Med 161: 475-489
52. Lee J, Yamamoto T, Kuramoto H et al (2012) TRPV1 expressing extrinsic primary sensory neurons play a protective role in mouse oxazolone-induced colitis. Auton Neurosci 166: 72-76
53. Linden DR, Couvrette JM, Ciolino A et al (2005) Indiscriminate loss of myenteric neurones in the TNBS-inflamed guinea-pig distal colon. Neurogastroenterol Motil 17: 751-760
54. Liu T, Ji R-R (2013) New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms? Pflugers Arch 465(12): 1671-1685. doi:10.1007/s00424-013-1284-2
55. Liu Q, Weng H-J, Patel KN et al (2011) The distinct roles of two GPCRs, MrgprC11 and PAR2, in itch and hyperalgesia. Sci Signal 4:ra45
56. Madden KB, Whitman L, Sullivan C et al (2002) Role of STAT6 and mast cells in IL-4- and IL-13-induced alterations in murine intestinal epithelial cell function. J Immunol 169: 4417-4422
57. Man Angela L, Bertelli E, Rentini S et al (2015) Age-associated modifications of intestinal permeability and innate immunity in human small intestine. Clin Sci 129: 515-527
58. Manel N, Unutmaz D, Littman DR (2008) The differentiation of human TH-17 cells requires transforming growth factor-[beta] and induction of the nuclear receptor ROR[gamma]t. Nat Immunol 9: 641-649
59. Margolis KG, Karamooz N, Stevanovic K et al (2011) Enteric neuronal density contributes to the severity of intestinal inflammation. Gastroenterology 141:588-598.e2
60. Matteoli G, Gomez-Pinilla PJ, NemethovaA et al (2014) A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut 63: 938-948
61. MaweGM (2015) Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon. J Clin Invest 125:949-955
62. McLean LP, Smith A, Cheung L et al (2015) Type 3 muscarinic receptors contribute to clearance of Citrobacter rodentium. Inflamm Bowel Dis 21: 1860-1871
63. Meir M, Flemming S, Burkard N et al (2015) Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro. Am J Physiol Gastrointest Liver Physiol 309: G613-G624
64. Merrell AJ, Stanger BZ (2016) Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style. Nat Rev Mol Cell Biol 17: 413-425
65. Monticelli LA, Osborne LC, Noti M et al (2015) IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci U S A 112: 10762-10767
66. Mueller SN, Gebhardt T, Carbone FR et al (2013) Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol 31: 137-161
67. Muller Paul A, Koscsó B, Rajani Gaurav M et al (2014) Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158: 300-313
68. Murphy CA, Langrish CL, Chen Y et al (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198: 1951-1957
69. Neunlist M, Aubert P, Toquet C et al (2003) Changes in chemical coding of myenteric neurones in ulcerative colitis. Gut 52: 84-90
70. Neunlist M, Aubert P, Bonnaud S et al (2007) Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-β1-dependent pathway. Am J Physiol Gastrointest Liver Physiol 292: G231-G241
71. Neunlist M, Van Landeghem L, Mahe MM et al (2013) The digestive neuronal-glial-epithelial unit: a new actor in gut health and disease. Nat Rev Gastroenterol Hepatol 10: 90-100
72. Neunlist M, Rolli-Derkinderen M, Latorre R et al (2014) Enteric glial cells: recent developments and future directions. Gastroenterology 147: 1230-1237
73. Nielsen OH, Kirman I, Rudiger N et al (2003) Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Scand J Gastroenterol 38: 180-185
74. Notari L, Riera DC, Sun R et al (2014) Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection. PLoS One 9: e84763
75. Nussbaum JC, Van Dyken SJ, von Moltke J et al (2013) Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502: 245-248
76. O’Sullivan D, Pearce EL (2015) Targeting T cell metabolism for therapy. Trends Immunol 36: 71-80
77. Olofsson PS, Rosas-Ballina M, Levine YA et al (2012) Rethinking inflammation: neural circuits in the regulation of immunity. Immunol Rev 248: 188-204
78. Ordovas-Montanes J, Rakoff-Nahoum S, Huang S et al (2015) The regulation of immunological processes by peripheral neurons in homeostasis and disease. Trends Immunol 36: 578-604
79. Owyang AM, Zaph C, Wilson EH et al (2006) Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med 203: 843-849
80. Pastorelli L, De Salvo C, Mercado JR et al (2013) Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol 4: 280
81. Pochard C, Coquenlorge S, Jaulin J et al (2016) Defects in 15-HETE production and control of epithelial permeability by human enteric glial cells from patients with Crohn’s disease. Gastroenterology 150: 168-180
82. Pongratz G, Straub RH (2014) The sympathetic nervous response in inflammation. Arthritis Res Ther 16: 504
83. Reading NC, Kasper DL (2011) The starting lineup: key microbial players in intestinal immunity and homeostasis. Front Microbiol 2: 148
84. Rodrigo P, Erick R, Alexis MK (2010) Emerging evidence for the role of neurotransmitters in the modulation of T cell responses to cognate ligands. Cent Nerv Syst Agents Med Chem 10: 65-83
85. Rosas-Ballina M, Olofsson PS, Ochani M et al (2011) Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334: 98-101
86. Sanders VM, Baker RA, Ramer-Quinn DS et al (1997) Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help. J Immunol 158: 4200-4210
87. Savidge TC, Newman P, Pothoulakis C et al (2007) Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology 132: 1344-1358
88. Sedda S, Marafini I, Figliuzzi MM et al (2014) An overview of the role of innate lymphoid cells in gut infections and inflammation. Mediators Inflamm 2014: 235460
89. Sharkey KA, Savidge TC (2014) Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract. Auton Neurosci 181: 94-106
90. Sharma S, Thomas PG (2014) The two faces of heterologous immunity: protection or immunopathology. J Leukoc Biol 95: 405-416
91. Shea-Donohue T, Urban JF Jr (2004) Gastrointestinal parasite and host interactions. Curr Opin Gastroenterol 20: 3-9
92. Shea-Donohue T, Sullivan C, Finkelman FD et al (2001) The role of IL-4 in Heligmosomoidespolygyrus-induced alterations in murine intestinal epithelial cell function. J Immunol 167: 2234-2239
93. Shea-Donohue T, Fasano A, Smith A et al (2010a) Enteric pathogens and gut function: role of cytokines and STATs. Gut Microbes 1: 316-324
94. Shea-Donohue T, Stiltz J, Zhao A et al (2010b) Mast cells. Curr Gastroenterol Rep 12: 349-357
95. Shea-Donohue T, Notari L, Stiltz J et al (2010c) Role of enteric nerves in immune-mediated changes in protease-activated receptor 2 effects on gut function. Neurogastroenterol Motil 22: 1138-e291
96. Shi H, Kokoeva MV, Inouye K et al (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Investig 116: 3015-3025
97. Shih H-Y, Sciumè G, Mikami Y et al (2016) Developmental acquisition of regulomes underlies innate lymphoid cell functionality. Cell 165: 1120-1133
98. Sipos F, Leiszter K, Tulassay Z (2011) Effect of ageing on colonic mucosal regeneration. World J Gastroenterol 17: 2981-2986
99. Snoek SA, Verstege MI, van der Zanden EP et al (2010) Selective α7 nicotinic acetylcholine receptor agonists worsen disease in experimental colitis. Br J Pharmacol 160: 322-333
100. Sonnenberg GF, Artis D (2015) Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med 21: 698-708
101. Stead RH (1992) Innervation of mucosal immune cells in the gastrointestinal tract. Reg Immunol 4: 91-99
102. Straub RH, Wiest R, Strauch UG et al (2006) The role of the sympathetic nervous system in intestinal inflammation. Gut 55: 1640-1649
103. Sun R, Urban JF, Notari L et al (2016) Interleukin-13 receptor α1-dependent responses in the intestine are critical to parasite clearance. Infect Immun 84: 1032-1044
104. Sundin J, Rangel I, Kumawat AK et al (2014) Aberrant mucosal lymphocyte number and subsets in the colon of post-infectious irritable bowel syndrome patients. Scand J Gastroenterol 49: 1068-1075
105. Takahara M, Nemoto Y, Oshima S et al (2013) IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice. Immunol Lett 156: 82-93
106. Thaiss CA, Zmora N, Levy M et al (2016) The microbiome and innate immunity. Nature 535: 65-74
107. Tournier J-N, Hellmann AQ (2003) Neuro-immune connections: evidence for a neuro-immunological synapse. Trends Immunol 24: 114-115
108. Tracey KJ (2002) The inflammatory reflex. Nature 420: 853-859
109. Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Investig 117: 289-296
110. Vasina V, Abu-gharbieh E, Barbara G et al (2008) The β3-adrenoceptor agonist SR58611A ameliorates experimental colitis in rats. Neurogastroenterol Motil 20: 1030-1041
111. Verburg-van Kemenade BM, Cohen N, Chadzinska M (2017) Neuroendocrine-immune interaction: evolutionarily conserved mechanisms that maintain allostasis in an ever-changing environment. Dev Comp Immunol 66: 2-23
112. Vergnolle N (2016) Protease inhibition as new therapeutic strategy for GI diseases. Gut 65: 1215-1224
113. Vignali DAA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8: 523-532
114. Volpe E, Servant N, Zollinger R et al (2008) A critical function for transforming growth factor-[beta], interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses. Nat Immunol 9: 650-657
115. von Moltke J, Ji M, Liang H-E et al (2016) Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529: 221-225
116. Wang H, Yu M, Ochani M et al (2003) Nicotinic acetylcholine receptor [alpha]7 subunit is an essential regulator of inflammation. Nature 421: 384-388
117. Wang G-D, Wang X-Y, Liu S et al (2014) Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine. Am J Physiol Gastrointest Liver Physiol 307: G719-G731
118. Wang Z, Yang WL, Jacob A et al (2015) Human ghrelin mitigates intestinal injury and mortality after whole body irradiation in rats. PLoS One 10: e0118213
119. Weaver CT, Hatton RD, Mangan PR et al (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25: 821-852
120. Wilhelm C,Harrison OJ, Schmitt V et al (2016) Critical role of fatty acidmetabolism in ILC2-mediated barrier protection during malnutrition and helminth infection. J Exp Med 213: 1409-1418
121. Wilson SR, Thé L, Batia LM et al (2013) The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 155: 285-295
122. WuR, Dong W,Qiang X et al (2009) Orexigenic hormone ghrelin ameliorates gut barrier dysfunction in sepsis in rats. Crit Care Med 37: 2421-2426
123. Yona S, Kim K-W, Wolf Y et al (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38: 79-91
124. Zhao A, McDermott J, Urban JF Jr et al (2003) Dependence of IL-4, IL-13, and nematode-induced alterations in murine small intestinal smooth muscle contractility on Stat6 and enteric nerves. J Immunol 171: 948-954
125. Zhao J-F, Ching L-C, Kou YR et al (2013) Activation of TRPV1 prevents OxLDL-induced lipid accumulation and TNF-α-induced inflammation in macrophages: role of liver X receptor α. Mediators Inflamm 2013: 925171
126. Zhao Z-Q, Liu X-Y, Jeffry J et al (2014) Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling. Neuron 84: 821-834
127. Zigmond E, Varol C, Farache J et al (2012) Ly6Chi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37: 1076-1090
128. Zorzi F, Monteleone I, Sarra M et al (2013) Distinct profiles of effector cytokines mark the different phases of Crohn’s disease. PLoS One 8: e54562