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Autoimmunity in Dry Eye Is Due to Resistance of Th17 to Treg Suppression¹

Sunil K. Chauhan^*, Jaafar El Annan^2,*, Tatiana Ecoiffier^2,*, Sunali Goyal^*, Qiang Zhang^*, Daniel R. Saban^* and Reza Dana^3,*,

^* Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114; and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grant NEI R01-12963.

² J.E. and T.E. contributed equally and share second authorship.

³ Address correspondence and reprint requests to Dr. Reza Dana, Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114. E-mail address: reza.dana{at}schepens.harvard.edu

⁴ Abbreviations used in this paper: DED, dry eye disease; CEC, controlled-environment chamber; IL-17RA, IL-17 receptor A; LN, lymph node; Treg, T regulatory cell; Tresp, responder CD4⁺ T.

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