Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep. 2023 Feb 28;42(2):112073. doi: 10.1016/j.celrep.2023.112073. Epub 2023 Feb 2.
Type 2 T helper (Th2) cells and group 2 innate lymphoid cells (ILC2s) provide protection against helminth infection and are involved in allergic responses. However, their relative importance and crosstalk during type 2 immune responses are still controversial. By generating and utilizing mouse strains that are deficient in either ILC2s or Th2 cells, we report that interleukin (IL)-33-mediated ILC2 activation promotes the Th2 cell response to papain; however, the Th2 cell response to ovalbumin (OVA)/alum immunization is thymic stromal lymphopoietin (TSLP) dependent but independent of ILC2s. During helminth infection, ILC2s and Th2 cells collaborate at different phases of the immune responses. Th2 cells, mainly through IL-4 production, induce the expression of IL-25, IL-33, and TSLP, among which IL-25 and IL-33 redundantly promote ILC2 expansion. Thus, while Th2 cell differentiation can occur independently of ILC2s, activation of ILC2s may promote Th2 responses, and Th2 cells can expand ILC2s by inducing type 2 alarmins.
2 型 T 辅助（Th2）细胞和 2 型固有淋巴细胞（ILC2）为抵御寄生虫感染提供了保护，并参与过敏反应。然而，它们在 2 型免疫反应中的相对重要性和相互作用仍存在争议。通过生成和利用缺乏 ILC2 或 Th2 细胞的小鼠品系，我们报告白介素（IL）-33 介导的 ILC2 激活促进了木瓜蛋白酶诱导的 Th2 细胞反应；然而，卵清蛋白（OVA）/明矾免疫诱导的 Th2 细胞反应依赖于胸腺基质淋巴细胞生成素（TSLP），但不依赖于 ILC2。在寄生虫感染期间，ILC2 和 Th2 细胞在免疫反应的不同阶段协同作用。Th2 细胞主要通过产生 IL-4 诱导 IL-25、IL-33 和 TSLP 的表达，其中 IL-25 和 IL-33 可冗余地促进 ILC2 的扩增。因此，虽然 Th2 细胞分化可以独立于 ILC2 发生，但 ILC2 的激活可能会促进 Th2 反应，而 Th2 细胞可以通过诱导 2 型警报素来扩增 ILC2。
