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BIM determines the number of merocytic dendritic cells, a cell type that breaks immune tolerance
Author(s) -
Audiger Cindy,
Lesage Sylvie
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12165
Subject(s) - autoimmunity , immune system , dendritic cell , locus (genetics) , biology , immunology , nod , t cell , gene , microbiology and biotechnology , haematopoiesis , type 1 diabetes , genetics , diabetes mellitus , stem cell , endocrinology
In contrast to conventional dendritic cells ( cDC ), when merocytic dendritic cells (mc DC ) present antigens derived from apoptotic bodies, T‐cell anergy is reversed rather than induced, a process that promotes autoimmunity. Interestingly, mc DC are present in higher proportion in type 1 diabetes‐prone NOD mice than in autoimmune‐resistant B6 and BALB /c mice, and the Insulin‐dependent diabetes (Idd)13 locus is linked to mc DC proportion. Therefore, mc DC are notably associated with susceptibility to autoimmune diabetes. To identify which gene determines the proportion and absolute number of mc DC , we undertook a candidate gene approach by selecting relevant candidates within the Idd13 locus. We find that neither β2m nor Sirpa appear to influence the proportion of mc DC . Instead, we show that Bim effectively modulates mc DC number in a hematopoietic‐intrinsic manner. We also demonstrate that Bim ‐deficiency does not impact other cDC subsets and appears to play a specific role in determining the proportion and absolute number of mc DC by promoting their survival. Together, these data demonstrate that Bim specifically modulates the number of mc DC . Identifying factors that facilitate apoptosis of mc DC by increasing BIM activity in a cell type‐specific manner may help prevent autoimmunity.