Liang Spencer C, Tan Xiang-Yang, Luxenberg Deborah P, Karim Riyez, Dunussi-Joannopoulos Kyriaki, Collins Mary, Fouser Lynette A
Wyeth Research, Cambridge, MA 02140, USA.
J Exp Med. 2006 Oct 2;203(10):2271-9. doi: 10.1084/jem.20061308. Epub 2006 Sep 18.
Th17 cells are a distinct lineage of effector CD4(+) T cells characterized by their production of interleukin (IL)-17. We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by transforming growth factor beta signaling in the context of IL-6 and other proinflammatory cytokines. The subsequent expansion of IL-22-producing cells was dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F. To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in conjunction with IL-17A or IL-17F synergistically induced the expression of beta-defensin 2 and S100A9 and additively enhanced the expression of S100A7 and S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity.
辅助性T细胞17（Th17细胞）是效应性CD4(+) T细胞的一个独特亚群，其特征是产生白细胞介素（IL）-17。我们证明，Th17细胞也表达IL-22（一种IL-10家族成员），其表达量显著高于辅助性T细胞（Th）1或Th2细胞。与IL-17A相似，IL-22的表达是在IL-6和其他促炎细胞因子的背景下由转化生长因子β信号通路启动的。随后产生IL-22的细胞的扩增依赖于IL-23。我们进一步证明，IL-22在体外和体内均与IL-17A和IL-17F共表达。为了研究这些细胞因子之间的功能关系，我们检测了用IL-22、IL-17A和IL-17F组合处理的原代角质形成细胞中抗菌肽的表达。IL-22与IL-17A或IL-17F协同诱导β-防御素2和S100A9的表达，并累加增强S100A7和S100A8的表达。总的来说，我们已确定IL-22是Th17细胞表达的一种新细胞因子，它与IL-17A或IL-17F协同作用以调节与皮肤固有免疫相关的基因。
