新西兰马拉根医学研究所Franca Ronchese团队发现，健康皮肤中的稳态IL-13指导树突状细胞分化来促进T_H2和抑制T_H17细胞极化。该研究于2021年11月18日在线发表于国际一流学术期刊《自然—免疫学》。

研究人员表明，CD11b^lo迁移性2型树突状细胞（DC2）的分化，这是一种皮肤特有的DC2群体，需要依赖于转录因子STAT6和KLF4的IL-13信号，而肺和小肠的DC2则不依赖于STAT6。同样，人类皮肤中的DC2表达了IL-4和IL-13基因特征，而在血液、脾脏和肺部DC中没有发现。在小鼠中，IL-13是由皮肤先天性淋巴细胞匀速分泌的，与微生物群、TSLP或IL-33无关。在没有IL-13信号的情况下，皮肤DC2的数量稳定，但仍然是CD11b^hi，并在对过敏原的反应中显示出有缺陷的激活，支持IL-4⁺GATA3⁺辅助T细胞（T_H）发育的能力减弱，而抗真菌的IL-17⁺RORγt⁺T_H细胞则增加。因此，稳态的IL-13促进了非炎症性的皮肤环境，从而支持过敏性致敏。

据了解，驱动DC2适应不同外周环境的信号大多仍未确定。

附：英文原文

Title: Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization

Author: Mayer, Johannes U., Hilligan, Kerry L., Chandler, Jodie S., Eccles, David A., Old, Samuel I., Domingues, Rita G., Yang, Jianping, Webb, Greta R., Munoz-Erazo, Luis, Hyde, Evelyn J., Wakelin, Kirsty A., Tang, Shiau-Choot, Chappell, Sally C., von Daake, Sventja, Brombacher, Frank, Mackay, Charles R., Sher, Alan, Tussiwand, Roxane, Connor, Lisa M., Gallego-Ortega, David, Jankovic, Dragana, Le Gros, Graham, Hepworth, Matthew R., Lamiable, Olivier, Ronchese, Franca

Issue&Volume: 2021-11-18

Abstract: The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s—a DC2 population unique to the dermis—required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.

DOI: 10.1038/s41590-021-01067-0

Source: https://www.nature.com/articles/s41590-021-01067-0