VISTA Blockade Aggravates Bone Loss in Experimental Murine Apical Periodontitis

Front Immunol. 2021 Oct 7:12:738586. doi: 10.3389/fimmu.2021.738586. eCollection 2021.

Abstract

V-domain Ig suppressor of T cell activation (VISTA) is a novel coinhibitory immune checkpoint molecule that maintains immune homeostasis. The present study explored the role of VISTA in human and murine inflammatory tissues of apical periodontitis (AP). VISTA was upregulated in inflammatory tissues of human AP. In mice, the expression of VISTA gradually increased with the development of mouse experimental apical periodontitis (MAP), the CD3+ T cells, CD11b+ myeloid cells, and FOXP3+ regulatory T cells also gradually accumulated. Moreover, a blockade of VISTA using a mouse in vivo anti-VISTA antibody aggravated periapical bone loss and enhanced the infiltration of immune cells in an experimental mouse periapical periodontitis model. The collective results suggest that VISTA serves as a negative regulator of the development and bone loss of apical periodontitis.

Keywords: VISTA; apical periodontitis; bone loss; immune checkpoint; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alveolar Bone Loss / immunology
  • Alveolar Bone Loss / metabolism*
  • Alveolar Bone Loss / pathology
  • Alveolar Process / drug effects*
  • Alveolar Process / immunology
  • Alveolar Process / metabolism
  • Animals
  • Antibodies / toxicity*
  • B7 Antigens / metabolism
  • Case-Control Studies
  • Disease Models, Animal
  • Humans
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Periapical Periodontitis / immunology
  • Periapical Periodontitis / metabolism*
  • Periapical Periodontitis / pathology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Young Adult

Substances

  • Antibodies
  • B7 Antigens
  • Membrane Proteins
  • VSIR protein, human
  • Vsir protein, mouse