Sublingual macrophage-associated ILDR2 contributes to immune tolerance via Treg induction

Farzana Sultana, Amrita Widyagarini, Yohei Kawano, Yujin Ohsugi, Sayaka Katagiri, Miyuki Azuma, Shigenori Nagai

Research output: Contribution to journalArticlepeer-review

Abstract

The sublingual mucosa (SLM) has been used for sublingual immunotherapy (SLIT) which has the potential to induce antigen-specific immune tolerance. We previously demonstrated the CD206+ macrophages that were increased in the SLM after repeated antigen exposure. These macrophages showed high expression of the gene encoding ILDR2 (Ig-like domain-containing receptor 2), an immune checkpoint molecule. Here, we found a subpopulation of SLM CD206hi macrophages expressed cell surface ILDR2, using a newly developed monoclonal antibody that was specific to mouse ILDR2. ILDR2 expression in the CD206+ macrophages was restricted to the SLM, and the percentage of CD206hiILDR2+ macrophages increased after the repeated antigen painting. RNA-seq analysis revealed that this CD206hiILDR2+ fraction displayed downregulated expression of pro-inflammatory genes and preferentially expressed M2 macrophage related genes. This CD206hiILDR2+ fraction preferentially increased Foxp3+ regulatory T cells (Tregs) from naive CD4+ T cell coculture in vitro, and the induction of Tregs was blocked by a neutralizing anti-TGF-β antibody. Our results demonstrated that ILDR2-expressed in the SLM CD206+ macrophages contribute to immune tolerance by generating Tregs in a TGF-β dependent manner.

Original languageEnglish
Article number151009
JournalBiochemical and Biophysical Research Communications
Volume742
DOIs
Publication statusPublished - Jan 2025

Keywords

  • CD206 macrophages
  • Foxp3 regulatory T cells
  • ILDR2
  • Immune tolerance
  • TGF-β

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