Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation.

Xiao S, Brooks CR, Sobel RA, Kuchroo VK
J Immunol. 2015 194 (4): 1602-8

PMID: 25582854 · PMCID: PMC4346345 · DOI:10.4049/jimmunol.1402632

T cell Ig and mucin domain (Tim)-1 identifies IL-10-producing regulatory B cells (Bregs). Mice on the C57BL/6 background harboring a loss-of-function Tim-1 mutant showed progressive loss of IL-10 production in B cells and with age developed severe multiorgan tissue inflammation. We demonstrate that Tim-1 expression and signaling in Bregs are required for optimal production of IL-10. B cells with Tim-1 defects have impaired IL-10 production but increased proinflammatory cytokine production, including IL-1 and IL-6. Tim-1-deficient B cells promote Th1 and Th17 responses but inhibit the generation of regulatory T cells (Foxp3(+) and IL-10-producing type 1 regulatory T cells) and enhance the severity of experimental autoimmune encephalomyelitis. Mechanistically, Tim-1 on Bregs is required for apoptotic cell (AC) binding to Bregs and for AC-induced IL-10 production in Bregs. Treatment with ACs reduces the severity of experimental autoimmune encephalomyelitis in hosts with wild-type but not Tim-1-deficient Bregs. Collectively, these findings suggest that in addition to serving as a marker for identifying IL-10-producing Bregs, Tim-1 is also critical for maintaining self-tolerance by regulating IL-10 production in Bregs.

Copyright © 2015 by The American Association of Immunologists, Inc.

MeSH Terms (14)

Animals B-Lymphocytes, Regulatory Encephalomyelitis, Autoimmune, Experimental Flow Cytometry Hepatitis A Virus Cellular Receptor 1 Inflammation Interleukin-10 Lymphocyte Activation Membrane Proteins Mice Mice, Inbred C57BL Mice, Mutant Strains Real-Time Polymerase Chain Reaction Self Tolerance

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