TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease

J Immunol. 2016 May 1;196(9):3570-80. doi: 10.4049/jimmunol.1501591. Epub 2016 Mar 25.

Abstract

T cell Ig and ITIM domain receptor (TIGIT), expressed on T, NK, and regulatory T cells, is known as an inhibitory molecule that limits autoimmunity, antiviral and antitumor immunity. In this report, we demonstrate that TIGIT enhances Th2 immunity. TIGIT expression was upregulated in activated Th2 cells from mice with experimental allergic disease and in Th2 polarization cultures. In addition, its high-affinity ligand CD155 was upregulated in mediastinal lymph node dendritic cells from allergic mice. In an in vitro setting, we observed that Tigit expression in Th2 cells and its interaction with CD155 expressed in dendritic cells were important during the development of Th2 responses. In addition, blockade of TIGIT inhibited Th2, but had no effect on either Th1 or Th17 polarization. In vivo blockade of TIGIT suppressed hallmarks of allergic airway disease, such as lung eosinophilia, goblet cell hyperplasia, Ag-specific Th2 responses, and IgE production, and reduced numbers of T follicular helper and effector Th2 cells. Thus, TIGIT is critical for Th2 immunity and can be used as a therapeutic target, especially in light of recent findings showing TIGIT locus hypomethylation in T cells from pediatric patients with allergic asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Female
  • Goblet Cells / immunology
  • Hyperplasia / immunology
  • Hypersensitivity / immunology*
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin E / immunology
  • Immunologic Memory*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Eosinophilia / immunology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Virus / genetics
  • Th17 Cells / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / physiology

Substances

  • Cytokines
  • Receptors, Immunologic
  • Receptors, Virus
  • T cell Ig and ITIM domain protein, mouse
  • poliovirus receptor
  • Immunoglobulin E