ILDR2-Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Immune Tolerance

J Immunol. 2018 Mar 15;200(6):2013-2024. doi: 10.4049/jimmunol.1700326. Epub 2018 Feb 5.

Abstract

ILDR2 is a member of the Ig superfamily, which is implicated in tricellular tight junctions, and has a putative role in pancreatic islet health and survival. We recently found a novel role for ILDR2 in delivering inhibitory signals to T cells. In this article, we show that short-term treatment with ILDR2-Fc results in long-term durable beneficial effects in the relapsing-remitting experimental autoimmune encephalomyelitis and NOD type 1 diabetes models. ILDR2-Fc also promotes transplant engraftment in a minor mismatch bone marrow transplantation model. ILDR2-Fc displays a unique mode of action, combining immunomodulation, regulation of immune homeostasis, and re-establishment of Ag-specific immune tolerance via regulatory T cell induction. These findings support the potential of ILDR-Fc to provide a promising therapeutic approach for the treatment of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology*
  • Bone Marrow Transplantation / methods
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Homeostasis / immunology*
  • Immune Tolerance / immunology*
  • Immunoglobulin Fc Fragments / immunology*
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD

Substances

  • Antigens
  • ILDR2 protein, mouse
  • Immunoglobulin Fc Fragments
  • Membrane Proteins