Angkasekwinai Pornpimon, Sodthawon Wichuda, Jeerawattanawart Siranart, Hansakon Adithap, Pattanapanyasat Kovit, Wang Yui-Hsi
Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani Thailand.
Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani Thailand.
PLoS One. 2017 Sep 12;12(9):e0184684. doi: 10.1371/journal.pone.0184684. eCollection 2017.
IL-25, an IL-17 family cytokine, derived from epithelial cells was shown to regulate Th2- and Th9-type immune responses. We previously reported that IL-25 was important in promoting efficient protective immunity against T. spiralis infection; however, the cellular targets of IL-25 to elicit type-2 immunity during infection have not yet been addressed. Here, we investigated IL-25-responding cells and their involvement in mediating type-2 immune response during T. spiralis infection. ILC2 and CD4+ Th2 cells residing in the gastrointestinal tract of T. spiralis infected mice were found to express high levels of surface interleukin-17 receptor B (IL-17RB), a component of the IL-25 receptor. Following T. spiralis infection, activated ILC2s upregulated surface MHCII expression and enhanced capacity of effector T helper cell in producing antigen-specific Th2 and Th9 cytokines through MHCII-dependent interactions. Reciprocally, lack of CD4+ T helper cells impaired ILC2 function to produce type 2-associated cytokines in responding to IL-25 during T. spiralis infection. Furthermore, mice deficient in IL-17RB showed markedly reduced ILC2 numbers and antigen-specific Th2 and Th9 cytokine production during T. spiralis infection. The Il17rb-/- mice failed to mount effective antigen specific Th2 and Th9 functions resulting in diminished goblet cell and mast cell responses, leading to delayed worm expulsion in the intestines and muscles. Thus, our data indicated that ILC2s and CD4+ Th2 cells are the predominant cellular targets of IL-25 following T. spiralis infection and their collaborative interactions may play a key role in mounting effective antigen-specific Th2 and Th9 cytokine responses against T. spiralis infection.
白细胞介素-25（IL-25）是一种源自上皮细胞的白细胞介素-17家族细胞因子，已被证明可调节2型和9型免疫反应。我们之前报道过，IL-25在促进针对旋毛虫感染的有效保护性免疫方面很重要；然而，IL-25在感染期间引发2型免疫的细胞靶点尚未得到研究。在这里，我们研究了对IL-25有反应的细胞及其在旋毛虫感染期间介导2型免疫反应中的作用。我们发现，感染旋毛虫的小鼠胃肠道中的2型固有淋巴细胞（ILC2）和CD4 +辅助性T细胞2（Th2细胞）表达高水平的表面白细胞介素-17受体B（IL-17RB），它是IL-25受体的一个组成部分。旋毛虫感染后，活化的ILC2上调表面主要组织相容性复合体II类分子（MHCII）的表达，并通过MHCII依赖性相互作用增强效应性辅助性T细胞产生抗原特异性Th2和Th9细胞因子的能力。相反，缺乏CD4 +辅助性T细胞会损害ILC2在旋毛虫感染期间对IL-25产生2型相关细胞因子的功能。此外，IL-17RB缺陷的小鼠在旋毛虫感染期间显示ILC2数量明显减少，抗原特异性Th2和Th9细胞因子产生也减少。Il17rb-/-小鼠无法产生有效的抗原特异性Th2和Th9功能，导致杯状细胞和肥大细胞反应减弱，从而导致肠道和肌肉中蠕虫排出延迟。因此，我们的数据表明，ILC2和CD4 + Th2细胞是旋毛虫感染后IL-25的主要细胞靶点及其协同相互作用可能在针对旋毛虫感染产生有效的抗原特异性Th2和Th9细胞因子反应中起关键作用。
