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 II^hiCD86⁺ 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.

中文翻译：

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CD206+巨噬细胞的致耐受特性在反复抗原涂刷后出现在舌下黏膜中。

口腔中的舌下粘膜 (SLM) 被用作舌下免疫治疗的部位，以诱导对过敏原的耐受性。我们以前报道过重复抗原（例如雪松花粉或异硫氰酸荧光素（FITC））涂漆后，CD206 ⁺圆形巨噬细胞样细胞在 SLM 中被诱导。在这项研究中，我们检查了在 SLM 上重复 FITC 涂漆诱导的 CD206 ⁺细胞的表型和功能特性。重复FITC涂漆后的CD206 ⁺细胞具有巨噬细胞样CD11b ⁺ Ly6C ⁺ F4/80 ⁺ CD64 ⁺表型并高水平表达 TIM-4，该 TIM-4 在致耐受性组织驻留巨噬细胞中表达。根据微阵列分析评估，SLM CD206 ⁺细胞优先表达与内吞作用和稳态过程相关的分子，包括新型 B7 免疫检查点分子家族。SLM CD206 ⁺细胞显示优先表达 M2 相关基因，例如Fizz1、Aldh1a1和Aldh1a2，但不表达Ym-1和精氨酸酶-1。CD206 ⁺细胞丰富的状态抑制了 OVA 特异性 CD4 ⁺ T 细胞反应，但反过来提高了 IL-10 ⁺ CD4的比例⁺细胞和 Foxp3 ⁺区域淋巴结中的调节性 T 细胞。CD206 ⁺细胞与树突细胞 (DC) 的共培养显示，DC 中 IL-12 的产生受到抑制，同时 MHC II 类^hi CD86 ⁺群体下降，后者通过中和 IL-10 而恢复。这些结果表明 SLM CD206 ⁺细胞显示出耐受性巨噬细胞的特征并下调成熟 DC 的抗原呈递细胞功能，从而抑制 CD4 ⁺ T 细胞反应。