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

被引：0

作者：

Sultana, Farzana ^{[1
,2
]}

Widyagarini, Amrita ^{[2
,5
]}

Kawano, Yohei ^{[2
,6
]}

Ohsugi, Yujin ^{[1
,3
,4
]}

Katagiri, Sayaka ^{[1
,3
]}

Azuma, Miyuki ^{[1
,2
]}

Nagai, Shigenori ^{[1
,2
]}

机构：

[1] Inst Sci Tokyo, Grad Sch Med & Dent Sci, Dept Oral Biol, 1-5-45 Bunkyo Ku, Tokyo 1138549, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Mol Immunol, Tokyo 1138549, Japan

[3] Oral Sci Ctr, Inst Sci Tokyo, Tokyo 1138549, Japan

[4] Harvard Med Sch, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02115 USA

[5] Univ Indonesia, Fac Dent, Dept Pediat Dent, Depok 16424, Indonesia

[6] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Immunol, Hiroshima 7348551, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2025年 / 742卷

基金：

日本学术振兴会;

关键词：

Immune tolerance; CD206+macrophages; ILDR2; TGF-beta; Foxp3+regulatory T cells; REGULATORY T-CELLS; COUNTER-RECEPTOR; TGF-BETA; ANTIGEN; IMMUNOTHERAPY;

D O I：

10.1016/j.bbrc.2024.151009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta antibody. Our results demonstrated that ILDR2-expressed in the SLM CD206+ macrophages contribute to immune tolerance by generating Tregs in a TGF-beta dependent manner.

引用

页数：7