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

被引:239
作者
Chauhan, Sunil K. [1 ]
El Annan, Jaafar [1 ]
Ecoiffier, Tatiana [1 ]
Goyal, Sunali [1 ]
Zhang, Qiang [1 ]
Saban, Daniel R. [1 ]
Dana, Reza [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA
[2] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA
基金
美国国家卫生研究院;
关键词
REGULATORY T-CELLS; KERATOCONJUNCTIVITIS SICCA; IMMUNOLOGICAL-TOLERANCE; TEAR FLUID; DISEASE; INFLAMMATION; ARTHRITIS; SJOGRENS; ENCEPHALOMYELITIS; INTERLEUKIN-1;
D O I
10.4049/jimmunol.182.3.1247
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 DIED, 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 DIED. 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 Journal of Immunology, 2009, 182: 1247-1252.
引用
收藏
页码:1247 / 1252
页数:6
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