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

Cell Rep. 2020 Jul 14;32(2):107892. doi: 10.1016/j.celrep.2020.107892.


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.

Keywords: Autoimmunity; B cells; Spontaneous inflammatory disorders; TIGIT; Tim-1; Tissue tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology
  • Animals
  • B-Lymphocytes / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Hepatitis A Virus Cellular Receptor 1 / metabolism*
  • Immunomodulation
  • Inflammation / pathology*
  • Interleukin-10 / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein
  • Organ Specificity*
  • Peptide Fragments
  • Receptors, Immunologic / metabolism*


  • Havcr1 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Immunologic
  • T cell Ig and ITIM domain protein, mouse
  • myelin oligodendrocyte glycoprotein (35-55)
  • Interleukin-10