Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation

Y. W. Ji, S. K. Mittal, H. S. Hwang, E. J. Chang, J. H. Lee, Y. Seo, A. Yeo, H. Noh, H. S. Lee, S. K. Chauhan, H. K. Lee

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13 Citations (Scopus)

Abstract

Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.

Original languageEnglish
Pages (from-to)1202-1210
Number of pages9
JournalMucosal Immunology
Volume10
Issue number5
DOIs
Publication statusPublished - 2017 Sep 1

Bibliographical note

Funding Information:
We thank Hyeon Chang Kim, MD, PhD (Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea) for excellent discussion that assisted in statistical analysis and Hyeong-jae Jeong, MT (Department of Pathology, Yonsei University College of Medicine, Seoul, Korea) for assistance in the preparation of histological specimens of LGs and corneoconjunctival tissues. This work was supported in part by grants from the Korea Health Industry Development Institute (HI13C0055 to H.K.L.) and National Institute of Health (EY024602 to S.K.C.).

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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