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Moon, Jae-Seung; Ho, Chun-Chang; Park, Jong-Hyun; Park, Kyungsoo; Shin, Bo-Young; Lee, Su-Hyeon; Sequeira, Ines; Mun, Chin Hee; Shin, Jin-Su; Kim, Jung-Ho; Kim, Beom Seok; Noh, Jin-Wook; Lee, Eui-Seon; Son, Ji Young; Kim, Yuna; lee, Yeji; Cho, Hee; So, SunHyeon; Park, Jiyoon; Choi, Eunsu; Oh, Jong-Won; Lee, Sang-Won; Morio, Tomohiro; Watt, Fiona M.; Seong, Rho Hyun; Lee, Sang-Kyou
Nature communications, 09/2023, Letnik: 14, Številka: 1Journal Article
Abstract Regulatory T cells (T reg ) are CD4 + T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4 + T cells, T reg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1 + subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1 - subpopulation. Lrig1-deficiency impairs the suppressive function of T reg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4 + Lrig1 + T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.
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