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Checkpoint receptor TIGIT expressed on Tim-1+ B cells regulates tissue inflammation

ABSTRACT: Tim-1, a phosphatidylserine receptor expressed on B cells induces IL-10 production by sensing apoptotic cells. Here we show that mice with B cell-specific Tim-1 deletion developed tissue inflammation in multiple organs including spontaneous paralysis with inflammation in the central nervous system (CNS). Transcriptomic analysis demonstrated that besides IL-10, Tim-1+ B cells also differentially expressed a number of co-inhibitory “checkpoint” receptors including TIGIT. Mice with B cell-specific TIGIT deletion developed spontaneous paralysis with CNS inflammation but with limited inflammation in other organs. Our findings suggest that Tim-1+ B cells are essential for maintaining self-tolerance and restraining tissue inflammation, and that Tim-1 dependent TIGIT expression on B cells is essential for maintaining CNS-specific tolerance. A possible critical role of AhR in regulating the B cell function is discussed, as we found that AhR is a top-ranked transcription factor expressed in Tim-1+ B cells and regulates their TIGIT and IL-10 expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE150786 | GEO | 2020/08/31

REPOSITORIES: GEO

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Checkpoint receptor TIGIT expressed on Tim-1+ B cells regulates tissue inflammation

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