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Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation.

Cell reports (2020-07-16)
Sheng Xiao, Lloyd Bod, Nathalie Pochet, Savithri Balasubramanian Kota, Dan Hu, Asaf Madi, Jessica Kilpatrick, Jingwen Shi, Allen Ho, Huiyuan Zhang, Raymond Sobel, Howard L Weiner, Terry B Strom, Francisco J Quintana, Nicole Joller, Vijay K Kuchroo
ABSTRACT

Tim-1, a phosphatidylserine receptor expressed on B cells, induces interleukin 10 (IL-10) production by sensing apoptotic cells. Here we show that mice with B cell-specific Tim-1 deletion develop tissue inflammation in multiple organs including spontaneous paralysis with inflammation in the central nervous system (CNS). Transcriptomic analysis demonstrates that besides IL-10, Tim-1+ B cells also differentially express a number of co-inhibitory checkpoint receptors including TIGIT. Mice with B cell-specific TIGIT deletion develop 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 signaling-dependent TIGIT expression on B cells is essential for maintaining CNS-specific tolerance. A possible critical role of aryl hydrocarbon receptor (AhR) in regulating the B cell function is discussed, as we find that AhR is among the preferentially expressed transcription factors in Tim-1+ B cells and regulates their TIGIT and IL-10 expression.

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