Targeting CD6 for the treatment of experimental autoimmune uveitis

Journal of Autoimmunity
Lingjun ZhangFeng Lin

Abstract

CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naïve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies. In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one o...Continue Reading

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Citations

May 18, 2018·Immunology·Lee I GarnerMarion H Brown
Mar 29, 2020·Journal for Immunotherapy of Cancer·Inês T SimõesFrancisco Lozano
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yankai WeiHong Nian
Apr 21, 2020·Arthritis & Rheumatology·Yan LiFeng Lin
Oct 31, 2020·The Journal of Experimental Medicine·Daiki MoriBernard Malissen
Dec 9, 2020·Cells·María Velasco-de AndrésFernando Aranda
Jan 27, 2021·JCI Insight·Jeffrey H RuthDavid A Fox

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