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- Title
Tolerogenic properties of CD206<sup>+</sup> macrophages appeared in the sublingual mucosa after repeated antigen-painting.
- Authors
Yang, Yue; Nagai, Shigenori; Kang, Siwen; Xia, Yulong; Kawano, Yohei; Miyake, Kensuke; Karasuyama, Hajime; Azuma, Miyuki
- Abstract
The sublingual mucosa (SLM) in the oral cavity is utilized as the site for sublingual immunotherapy to induce tolerance against allergens. We previously reported that CD206+ round-type macrophage-like cells were induced in the SLM after repeated antigen (e.g. cedar pollen or fluorescein isothiocyanate (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 a macrophage-like CD11b+Ly6C+ F4/80+CD64+ phenotype and expressed TIM-4, which was expressed in tolerogenic tissue-resident macrophages, at a high level. SLM CD206+ cells preferentially expressed molecules related to endocytosis and homeostatic processes, including the novel B7 family of immune checkpoint molecules, as assessed 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+ regulatory T-cells in regional lymph nodes. Co-culture of CD206+ cells with dendritic cells (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 antigen-presenting cell function of mature DCs resulting in the inhibition of CD4+ T-cell responses.
- Subjects
MACROPHAGES; MOUTH; SUBLINGUAL immunotherapy; MUCOUS membranes; FLUORESCEIN isothiocyanate
- Publication
International Immunology, 2020, Vol 32, Issue 8, p509
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxaa014