Skint8, a Novel B7 Family-Related Molecule, Negatively Regulates T Cell Responses

J Immunol. 2019 Jul 15;203(2):400-407. doi: 10.4049/jimmunol.1800639. Epub 2019 Jun 12.

Abstract

Immune responses are tightly controlled by T cell costimulatory and coinhibitory molecules. In this study, we identify Skint8 as a new member of the T cell coinhibitory group, whose extracellular domains share significant homology with existing B7 family members. Skint8 mRNA is expressed in resting and activated B cells, monocytes, and CD4 T cells. The Skint8 putative receptor is expressed on activated CD4 and CD8 T cells, B cells, monocytes and dendritic cells. Recombinant Skint8-IgG Fc fusion protein inhibits T cell proliferation, activation, and cytokine production in vitro. In vivo administration of Skint8-IgG Fc reduces T cell activation and alleviates experimental autoimmune encephalomyelitis in mice. The findings broaden our understanding of the regulation of immune responses and may have implications for treating immune-related diseases.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B7-1 Antigen / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / physiology
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Immunoglobulin G / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology
  • RNA, Messenger / immunology

Substances

  • B7-1 Antigen
  • Cytokines
  • Immunoglobulin G
  • RNA, Messenger