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

  • 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*
  • *Corresponding author for this work
  • Brigham and Women’s Hospital
  • Harvard University
  • Stanford University
  • University of Zurich

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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.

Original languageEnglish
Article number107892
JournalCell Reports
Volume32
Issue number2
DOIs
StatePublished - 14 Jul 2020
Externally publishedYes

Funding

FundersFunder number
National Institutes of HealthP01073748, P01AI045757, P01AI039671
National Institute of Allergy and Infectious DiseasesP01AI129880
NATIONAL MULTIPLE SCLEROSIS SOCIETYRG-1907-34686
Lupus Research Alliance332938
European Research Council677200
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungPP00P3_150663

    Keywords

    • Autoimmunity
    • B cells
    • Spontaneous inflammatory disorders
    • TIGIT
    • Tim-1
    • Tissue tolerance

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