Treatment of murine lupus with TIGIT-Ig

Clin Immunol. 2019 Jun;203:72-80. doi: 10.1016/j.clim.2019.04.007. Epub 2019 Apr 18.

Abstract

The TIGIT (T cell immunoreceptor with Ig and ITIM domains) protein is a co-inhibitory receptor that has been reported to suppress autoreactive T and B cells to trigger immunological tolerance. We generated a new recombinant protein by connecting the extracellular domain of murine TIGIT to the Fc region of the mouse immunoglobulin IgG2a. The fusion protein was then characterized. The results suggested that among mice with lupus that were treated with the TIGIT-Ig fusion protein, the onset of proteinuria was delayed, serum concentrations of autoantibodies, such as antinuclear antibodies, were reduced without a decrease in the total IgG concentrations, and the survival rate was significantly increased compared to those of the controls. In conclusion, TIGIT-Ig administration showed promising results for both the prevention and treatment of autoimmune diseases in mice. This indicates that treatment with recombinant human TIGIT-Ig shows promise as an effective way to treat human autoimmune diseases.

Keywords: Murine lupus; Targeted therapy; Tigit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Disease Models, Animal
  • Female
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin G / genetics
  • Immunotherapy / methods*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / therapy*
  • Lupus Nephritis / immunology
  • Lupus Nephritis / therapy*
  • Mice
  • Mice, Inbred NZB
  • Mice, SCID
  • Receptors, Immunologic / genetics*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / therapeutic use*

Substances

  • Antibodies, Antinuclear
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • T cell Ig and ITIM domain protein, mouse