Sehra Sarita, Yao Weiguo, Nguyen Evelyn T, Glosson-Byers Nicole L, Akhtar Nahid, Zhou Baohua, Kaplan Mark H
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
J Allergy Clin Immunol. 2015 Aug;136(2):433-40.e1. doi: 10.1016/j.jaci.2015.01.021. Epub 2015 Mar 5.
IL-9 is important for the growth and survival of mast cells. IL-9 is produced by T cells, natural killer T cells, mast cells, eosinophils, and innate lymphoid cells, although the cells required for mast cell accumulation during allergic inflammation remain undefined.
We sought to elucidate the role of TH9 cells in promoting mast cell accumulation in models of allergic lung inflammation.
Adoptive transfer of ovalbumin-specific TH2 and TH9 cells was used to assess the ability of each subset to mediate mast cell accumulation in tissues. Mast cell accumulation was assessed in wild-type mice and mice with PU.1-deficient T cells subjected to acute and chronic models of allergic inflammation.
Adoptive transfer experiments demonstrated that recipients of TH9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or TH2 recipients. Mast cell accumulation was dependent on IL-9, but not IL-13, a cytokine required for many aspects of allergic inflammation. In models of acute and chronic allergic inflammation, decreased IL-9 levels in mice with PU.1-deficient T cells corresponded to diminished tissue mast cell numbers and expression of mast cell proteases. Mice with PU.1-deficient T cells have defects in IL-9 production from CD4(+) T cells, but not natural killer T cells or innate lymphoid cells, suggesting a TH cell-dependent phenotype. Rag1(-/-) mice subjected to a chronic model of allergic inflammation displayed reduced mast cell infiltration comparable with accumulation in mice with PU.1-deficient T cells, emphasizing the importance of IL-9 produced by T cells in mast cell recruitment.
TH9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.
白细胞介素-9（IL-9）对肥大细胞的生长和存活至关重要。IL-9由T细胞、自然杀伤T细胞、肥大细胞、嗜酸性粒细胞和固有淋巴细胞产生，不过在过敏性炎症期间肥大细胞聚集所需的细胞仍不明确。
我们试图阐明辅助性T细胞9（TH9细胞）在过敏性肺部炎症模型中促进肥大细胞聚集的作用。
采用卵清蛋白特异性TH2细胞和TH9细胞的过继转移来评估每个亚群介导组织中肥大细胞聚集的能力。在野生型小鼠和T细胞缺乏PU.1的小鼠中，对急性和慢性过敏性炎症模型中的肥大细胞聚集情况进行评估。
过继转移实验表明，与对照组或接受TH2细胞的受体相比，接受TH9细胞的受体有明显更高的肥大细胞聚集以及肥大细胞蛋白酶表达。肥大细胞聚集依赖于IL-9，而非IL-13，IL-13是过敏性炎症许多方面所需的一种细胞因子。在急性和慢性过敏性炎症模型中，T细胞缺乏PU.1的小鼠体内IL-9水平降低，这与组织中肥大细胞数量减少以及肥大细胞蛋白酶表达降低相对应。T细胞缺乏PU.1的小鼠在CD4(+) T细胞产生IL-9方面存在缺陷，但自然杀伤T细胞或固有淋巴细胞则无此缺陷，提示其具有TH细胞依赖性表型。患有慢性过敏性炎症模型的重组激活基因1（Rag1）基因敲除小鼠表现出肥大细胞浸润减少，与T细胞缺乏PU.1的小鼠中的聚集情况相当，这强调了T细胞产生的IL-9在肥大细胞募集中的重要性。
在过敏性炎症模型中，TH9细胞是IL-9的主要来源，并且在肥大细胞聚集和激活中发挥重要作用。
