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

Int Immunol. 2020 Jul 28;32(8):509-518. doi: 10.1093/intimm/dxaa014.


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.

Keywords: C-type lectin; immune homeostasis; immune suppression; oral mucosa; tissue microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Cryptomeria / chemistry
  • Female
  • Fluorescein-5-isothiocyanate / chemistry
  • Lectins, C-Type / immunology*
  • Macrophages / immunology*
  • Mannose-Binding Lectins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mouth Floor / immunology
  • Mucous Membrane / immunology*
  • Pollen / immunology
  • Receptors, Cell Surface / immunology*


  • Allergens
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor
  • Fluorescein-5-isothiocyanate