title: Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression.
abstract: Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an incomplete understanding of its specific cellular and molecular pathogenic elements. Using a validated mouse model of DED, herein we functionally characterize the different T cell subsets, including regulatory T cells (Tregs) and pathogenic effector T cells, and determine their contribution to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg suppression in DED. In addition, we clearly show that in vivo blockade of IL-17 significantly reduces the severity and progression of disease, which is paralleled by a reduction in the expansion of Th17 cells and restoration of Treg function. Our findings elucidate involvement of a previously unknown pathogenic T cell subset (Th17) in DED that is associated specifically with Treg dysfunction and disease pathogenesis and suggest a new target for dry eye therapy.
authors.affiliation: Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Jaafar
authors.initials: J
authors.lastname: El Annan
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ecoiffier
authors.forename: Sunali
authors.initials: S
authors.lastname: Goyal
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D018450:Disease Progression; D015352:Dry Eye Syndromes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005260:Female; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000473:pathology
chemical_list: D006131:Growth Inhibitors; D020381:Interleukin-17