Evaluation of Genome-wide chromatin accessibility of BM T cell subsets [ATAC_TC]

Chromatin accessibility of bone marrow conventional T cells, pTregs, tTregs, BMAC-induced Tregs and in vitro-induced Tregs were compared Bone marrow (BM) harbors a large repertoire of regulatory T (Treg) cells, which are essential in hematopoiesis and peripheral tolerance. Treg cell accumulation in BM has been viewed as a consequence of preferential immigration of thymus-derived Treg cells. Here we report a novel subset of antigen presenting cells, which expresses the autoimmune regulator (Aire). These BM Aire-expressing cells resemble a subset of CD138+B220-TACI+Blimp-1+MHC-II+ plasma cells (pc-BMACs) and express a diverse repertoire of tissue-restricted self-antigens. pc-BMACs present self-antigens to na ve CD4+ T cells and can efficiently convert these into functionally competent CD25+Foxp3+ bona fide peripheral Treg cells (pTregs) capable of exerting immune suppression in vitro and in vivo. Aire expression may contribute to the tolerogenic function of pc-BMACs as it regulates the expression of genes involved in pTreg induction and function, including Icosl and retinoic acid synthesis-related genes, Aldh1a2 and Aldh1b1. Our data thus demonstrate an Aire-expressing plasma cell subset in the BM capable to promote peripheral tolerance by ectopically expressing tissue-restricted self-antigens and generating pTregs. Overall design: 6.5TCR (HA-specific CD4) T cells were transferred into Aire-HA host and bone marrow T cell subsets were sorted 14 days post transfer for comparison of their chromatin accessibility