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

 Yong Woo Ji  ;  Sharad K. Mittal  ;  Ho Sik Hwang  ;  Eun-Ju Chang  ;  Joon H. Lee  ;  Yuri Seo  ;  Areum Yeo  ;  Hyemi Noh  ;  Hye Sun Lee  ;  Sunil K. Chauhan  ;  Hyung Keun Lee 
 MUCOSAL IMMUNOLOGY, Vol.10(5) : 1202-1210, 2017 
Journal Title
Issue Date
Acinar Cells/immunology ; Adult ; Aged ; Animals ; Cross-Sectional Studies ; Dry Eye Syndromes/immunology ; Eye/pathology ; Female ; Humans ; Interleukin-17/metabolism ; Interleukins/genetics ; Interleukins/metabolism ; Lacrimal Apparatus/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Mucous Membrane/immunology ; Th17 Cells/immunology ; Transplantation Chimera
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.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Seo, Yuri(서유리)
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Ji, Yong Woo(지용우)
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