Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2013 Oct 17;39(4):744-57. doi: 10.1016/j.immuni.2013.07.020.
Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4⁺ effector T cells in type 2 immunity is incompletely defined. Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that demonstrated an essential role for this cytokine in the early type 2 immunity against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2 innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9 production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid worm expulsion, marked basophilia, and increased mast cell numbers in Rag2-deficient hosts. Taken together, our data show a critical and nonredundant role for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm infection.
2 型炎症细胞因子,包括白细胞介素-4(IL-4)、IL-5、IL-9 和 IL-13,驱动着针对寄生虫和过敏原的免疫的特征。白细胞介素-9(IL-9)是否在宿主保护性反应的启动中发挥重要作用存在争议,并且在 2 型免疫中,IL-9 产生的 CD4+效应 T 细胞与 IL-4 产生的 CD4+效应 T 细胞的重要性尚未完全确定。在此,我们生成了缺乏白细胞介素-9(IL-9)的和带有 IL-9 荧光报告基因的小鼠,证明了这种细胞因子在针对巴西旋毛虫的早期 2 型免疫中具有重要作用。辅助性 T 细胞 9(Th9)细胞和 2 型先天淋巴样细胞(ILC2)是感染诱导 IL-9 产生的主要来源,但是 Th9 细胞的过继转移而不是 Th2 细胞的过继转移,导致 Rag2 缺陷型宿主中迅速驱除蠕虫、显著嗜碱性粒细胞增多和肥大细胞数量增加。综上所述,我们的数据表明 Th9 细胞和 IL-9 在宿主保护性 2 型免疫中针对寄生虫感染具有关键且非冗余的作用。