Kleinschek Melanie A, Boniface Katia, Sadekova Svetlana, Grein Jeff, Murphy Erin E, Turner Scott P, Raskin Lisa, Desai Bela, Faubion William A, de Waal Malefyt Rene, Pierce Robert H, McClanahan Terrill, Kastelein Robert A
Department of Immunology, Schering-Plough Biopharma, Palo Alto, CA 94304, USA.
J Exp Med. 2009 Mar 16;206(3):525-34. doi: 10.1084/jem.20081712. Epub 2009 Mar 9.
The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161(+) CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn's disease (CD), these CD161(+) cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-23 receptor. CD161(+) CD4 T cells from CD patients readily produce IL-17 and interferon gamma upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1beta was required to enable IL-23-induced cytokine release. Circulating CD161(+) Th17 cells are imprinted for gut homing, as indicated by high levels of CC chemokine receptor 6 and integrin beta7 expression. Supporting their colitogenic phenotype, CD161(+) Th17 cells were found in increased numbers in the inflammatory infiltrate of CD lesions and induced expression of inflammatory mediators by intestinal cells. Our data identify CD161(+) CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation.
C型凝集素样受体CD161最近被描述为可促进T细胞扩增，它在人类CD4 T细胞的一个离散亚群上表达。然而，这类细胞的功能仍不清楚。我们现在证明，CD161(+) CD4 T细胞包含循环和驻留在肠道的辅助性T细胞17（Th17）细胞群体。在克罗恩病（CD）期间，这些CD161(+)细胞表现出活化的Th17表型，白细胞介素（IL）-17、IL-22和IL-23受体的表达增加表明了这一点。来自CD患者的CD161(+) CD4 T细胞在用IL-23刺激后很容易产生IL-17和干扰素γ，而在健康受试者中，需要额外的炎症刺激如IL-1β进行启动才能使IL-23诱导细胞因子释放。循环中的CD161(+) Th17细胞表现出肠道归巢倾向，CC趋化因子受体6和整合素β7的高表达表明了这一点。支持它们的致结肠炎表型的是，在CD病变的炎症浸润中发现CD161(+) Th17细胞数量增加，并且它们可诱导肠道细胞表达炎症介质。我们的数据确定CD161(+) CD4 T细胞是一个静止的Th17细胞库，可被IL-23激活并介导破坏性组织炎症。
