Olson Matthew R, Ulrich Benjamin J, Hummel Sarah A, Khan Ibrahim, Meuris Brice, Cherukuri Yesesri, Dent Alexander L, Janga Sarath Chandra, Kaplan Mark H
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202;
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202.
J Immunol. 2017 Jun 1;198(11):4352-4359. doi: 10.4049/jimmunol.1601792. Epub 2017 May 3.
IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine-secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.
白细胞介素-2（IL-2）是一种多效性细胞因子，可促进包括Th1、Th2和Th9细胞在内的Th细胞亚群的分化，但会损害Th17细胞和滤泡辅助性T细胞的发育。尽管所有极化的Th亚群都会在一定程度上产生IL-2，但效应T细胞再次受到刺激时IL-2如何影响细胞因子的产生尚不清楚。我们在本文中表明，高尔基体转运抑制剂（GTIs）可阻断IL-9的产生。从机制上讲，GTIs阻断了IL-2的分泌，而IL-2通常以旁分泌方式反馈以促进信号转导和转录激活因子5（STAT5）的激活及IL-9的产生。IL-2反馈对Th1或Th17特征性细胞因子的产生没有影响，但它促进了Th2和Th9相关细胞因子的表达。这些数据表明，使用GTIs会导致对2型细胞因子分泌细胞存在情况的低估，并突出了IL-2作为Th2和Th9细胞在体外和体内最佳细胞因子产生中的关键成分。
