title: Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation.
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.
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.|Cornea Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Y W
authors.initials: YW
authors.lastname: Ji
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Mittal
authors.affiliation: Department of Ophthalmology, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Chang
authors.affiliation: Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Seo
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: A
authors.initials: A
authors.lastname: Yeo
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Noh
authors.affiliation: Biostatistics Collaboration Unit, Medical Research Center, Yonsei University College of Medicine, Seoul. Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Chauhan
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.|Cornea Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H K
authors.initials: HK
authors.lastname: Lee
mesh_terms: D061354:Acinar Cells / Q000276:immunology*; D000328:Adult; D000368:Aged; D000818:Animals; D003430:Cross-Sectional Studies; D015352:Dry Eye Syndromes / Q000276:immunology*; D005123:Eye / Q000473:pathology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007765:Lacrimal Apparatus / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018183:Transplantation Chimera; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22