Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Commun Biol. 2020 Dec 7;3(1):742. doi: 10.1038/s42003-020-01466-3.
While sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4Foxp3 regulatory T (T) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4Foxp3 T cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4Foxp3 T cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b conventional dendritic cells.
虽然舌下免疫疗法 (SLIT) 被认为是治疗 1 型过敏的一种过敏原特异性治疗方法，但它如何控制过敏发病机制仍不清楚。在这里，我们展示了下颌下淋巴结 (ManLNs) 中常规树突状细胞在 SLIT 治疗小鼠过敏疾病中的有效性中的前提作用。常规树突状细胞或 CD4Foxp3 调节性 T (T) 细胞的缺乏会破坏 SLIT 对过敏疾病的保护作用。此外，舌下抗原应用主要在上游 ManLNs 中诱导抗原特异性 CD4Foxp3 T 细胞，在缺乏 cDC 的情况下，该细胞严重受损。在 ManLNs 中，迁移的 CD11b cDC 比其他常规树突状细胞亚群更有利于产生抗原特异性 CD4Foxp3 T 细胞，这反映在它们在促进该程序的耐受性特征方面的优势。因此，ManLNs 是触发粘膜耐受性的特权部位，介导 SLIT 对过敏疾病的保护作用，这需要迁移的 CD11b 常规树突状细胞的耐受形成。
