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City of Hope

J. Autoimmun., Apr 19 2024, 146 S0896-8411(24)00062-3 | https://doi.org/10.1016/j.jaut.2024.103228 The CD318/CD6 axis limits type 1 diabetes islet autoantigen-specific human T cell activation

Jeong-su Do ^a,d, David Arribas-Layton ^a,d, Jemily Juan ^c,d, Isaac Garcia c^,d, Sindhu Saraswathy ^c,d, Meirigeng Qi ^b,d, Enrique Montero ^c,d, Helena Reijonen ^a,d

^aDepartment of Immunology and Theranostics, Canada

^bDepartment of Translational Research and Cellular Therapeutics, Canada

^cDepartment of Molecular and Cellular Endocrinology, Canada

^dArthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, California, USA

Corresponding authors: Jeong-su Do, Helena Reijonen

Abstract

CD6 is a glycoprotein expressed on CD4 and CD8 T cells involved in immunoregulation. CD318 has been identified as a CD6 ligand. The role of CD318 in T cell immunity is restricted as it has only been investigated in a few mice autoimmune models but not in human diseases. CD318 expression was thought to be limited to mesenchymal-epithelial cells and, therefore, contribute to CD6-mediated T cell activation in the CD318-expressing tissue rather than through interaction with antigen-presenting cells. Here, we report CD318 expression in a subpopulation of CD318 ⁺ myeloid dendritic (mDC), whereas the other peripheral blood populations were CD318 negative. However, CD318 can be induced by activation: a subset of monocytes treated with LPS and IFNγ and in vitro monocyte derived DCs were CD318 ⁺. We also showed that recombinant CD318 inhibited T cell function. Strikingly, CD318 ⁺ DCs suppressed the proliferation of autoreactive T cells specific for GAD65, a well-known targeted self-antigen in Type 1 Diabetes (T1D). Our study provides new insight into the role of the CD318/CD6 axis in the immunopathogenesis of inflammation, suggesting a novel immunoregulatory role of CD318 in T cell-mediated autoimmune diseases and identifying a potential novel immune checkpoint inhibitor as a target for intervention in T1D which is an unmet therapeutic need.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-24)
연구진국외 연구진
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