Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis

Abstract

Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis. Next, we ask whether IL-19 contributes to T cells-mediated colitis. Here, we investigated the role of IL-19 in a mouse model of Th2 cell-mediated colitis. Inflammatory responses in IL-19-deficient mice were assessed using a Th2-mediated colitis induced by oxazolone. The colitis was evaluated by analyzing the body weight loss and histology of the colon. Lymph node cells were cultured in vitro to determine cytokine production. IL-19 knockout mice exacerbated oxazolone-induced colitis by stimulating the transport of inflammatory cells into the colon, and by increasing IgE production and the number of circulating eosinophil. The exacerbation of oxazolone-induced colonic inflammation following IL-19 knockout mice was accompanied by an increased production of IL-4 and IL-9, but no changes in the expression of IL-5 and IL-13 in lymph node cells. IL-19 plays an anti-inflammatory role in the Th2-mediated colitis model, suggesting that IL-19 may represent a potential therapeutic target for reducing colonic inflammation.

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Abbreviations

CD:

Crohn’s disease

DSS:

dextran sulfate sodium

HE:

hematoxylin and eosin

IBDs:

inflammatory bowel diseases

IFN:

interferon

KO:

IL-19-knockout

MPO:

myeloperoxidase

UC:

ulcerative colitis

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Acknowledgements

This work was supported by Grants-in-Aid for Young Scientists (B) 20780209 (Y.T.A.) and 23780300 (Y.T.A.) and was supported by Grant-in-Aid for Scientific Research (B) 25292174 (Y.T.A.).

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Correspondence to Yasu-Taka Azuma.

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Fujimoto, Y., Azuma, YT., Matsuo, Y. et al. Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis. Naunyn-Schmiedeberg's Arch Pharmacol 390, 261–268 (2017). https://doi.org/10.1007/s00210-016-1329-0

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Keywords

  • Il-19
  • Anti-inflammatory cytokine
  • Inflammatory bowel disease