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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE136648 | GEO | 2022/08/26

REPOSITORIES: GEO

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Assessment of genome-wide chromatin accessibility of subsets of bone marrow-resident antigen presenting cells [ATAC_BMACs]

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2022-08-26 | GSE136649 | GEO

A novel lineage of RORγt+ antigen presenting cells instructs microbiota-dependent regulatory T cell differentiation and tolerance during early life [multiome scRNA-seq]

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2011-06-22 | E-GEOD-30129 | biostudies-arrayexpress

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2015-05-19 | E-GEOD-65617 | biostudies-arrayexpress

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Project description:Thymic medullary epithelial cell (mTEC) expression of the autoimmune regulator AIRE, and of tissue-specific antigens, is controlled by members of the non-canonical NF-kB signalling pathway, including RelB and NF-kB2. Of the genes in this pathway, RelB-/- mice develop a particularly severe multi-organ autoimmune syndrome, resembling Foxp3-deficiency. RelB-/- mice have medullary atrophy and few mTECs but the mechanism is unknown. We show that RelB is required for expression of medullary chemokines and mTEC AIRE, selection of a diverse peripheral T cell repertoire, and for peripheral Foxp3+ Treg function. VÎ² families of T cells infiltrating diseased peripheral organs and thymic Treg were similarly skewed. Surprisingly, medullary atrophy results from intra-thymic granulocyte infiltration, consequent upon the Th2-mediated autoimmune disease. Dominant tolerance corrects thymic inflammatory disease and loss of thymic function. We demonstrate a reversible RelB-dependent inflammatory mechanism for loss of central tolerance associated with medullary atrophy. Thymi from 4 RelB+/- mice and 3 RelB-/- mice were profiled by microarays

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