Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting

Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting

Abstract

The sublingual mucosa (SLM) in the oral cavity is utilized as the site for sublingual immunotherapy to induce tolerance against allergen. We previously reported that CD206+ round-type macrophage-like cells were induced in the SLM after repeated antigen (e.g., cedar pollen or FITC)-painting. In this study, we examined the phenotypic and functional properties of CD206+ cells induced by repeated FITC-painting on the SLM. CD206+ cells after the repeated FITC-painting possessed macrophage-like CD11b+Ly6C+ F4/80+CD64+ phenotype and expressed TIM4, which was expressed in tolerogenic tissue-resident macrophages, at a high level. SLM CD206+ cells preferentially expressed molecules related to endocytosis and homeostatic process, including the novel B7 family of immune checkpoint molecules by microarray analyses. SLM CD206+ cells showed preferential expression of M2-related genes such as Fizz1, Aldh1a1 and Aldh1a2 but not Ym-1 and Arginase-1. A CD206+ cell-rich status inhibited OVA-specific CD4+ T cell responses but reciprocally enhanced the proportion of both IL-10+CD4+ cells and Foxp3+ Tregs in regional lymph nodes. Co-culture of CD206+ cells with DCs showed that IL-12 production was suppressed in DCs concurrent with the decline of the MHC class IIhiCD86+ population, which was restored by neutralization of IL-10. These results demonstrate SLM CD206+ cells show the feature of tolerogenic macrophages and down-regulate the APC function of mature DCs resulting in the inhibition of CD4+ T cell responses.

Journal Article

JOURNAL:
International Immunology

TITLE:
Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting.

DOI:
https://doi.org/10.1093/intimm/dxaa014

Correspondence to

NAGAI Shigenori, Ph.D., Professor
Molecular Immunology,
Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University(TMDU)
E-mail:nagai.mim(at)tmd.ac.jp


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