Department of Internal Medicine Yale University School of Medicine, New Haven, CT, USA.
Blood. 2010 Jan 21;115(3):530-40. doi: 10.1182/blood-2009-08-236521. Epub 2009 Nov 12.
In humans, interleukin-1beta (IL-1beta) has been suggested as an essential cytokine for developing IL-17- or IL-17A-producing CD4(+) T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4(+) T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4(+) T cells of human peripheral blood. IL-1RI(+) memory CD4(+) T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1beta is programmed in these cells via IL-1RI. Although CD4(+) T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-beta (TGF-beta) up-regulated IL-1RI expression on naive CD4(+) T cells, suggesting that IL-1RI(+) naive CD4(+) T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naive CD4(+) T cells was induced by IL-1beta and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.
在人类中，白细胞介素-1β（IL-1β）被认为是产生白细胞介素-17 或白细胞介素-17A 产生的 CD4+辅助性 T 细胞 17（Th17）细胞所必需的细胞因子。然而，关于白细胞介素-1 受体表达与 Th17 细胞分化的关系知之甚少。我们在此报告了存在 2 种具有和不具有白细胞介素-1 受体 I（IL-1RI）表达的不同 CD4+T 细胞群，这与在人类外周血的幼稚和记忆 CD4+T 细胞中产生白细胞介素-17 的能力相关。IL-1RI+记忆 CD4+T 细胞在 T 细胞受体触发之前就已经增加了白细胞介素-17、RORC 和 IRF4 的基因表达，这表明 IL-1β 的作用是通过 IL-1RI 在这些细胞中编程的。尽管脐带血中的 CD4+T 细胞不表达 IL-1RI，但细胞因子 IL-7、IL-15 和转化生长因子-β（TGF-β）上调了幼稚 CD4+T 细胞上的 IL-1RI 表达，这表明 IL-1RI+幼稚 CD4+T 细胞在外周发育。此外，用细胞因子处理的幼稚 CD4+T 细胞产生的白细胞介素-17 可被白细胞介素-1β诱导，而这种诱导可被白细胞介素-1 受体拮抗剂阻断。这些结果表明，人类 Th17 细胞分化是通过 IL-1RI 的差异表达来调节的，而 IL-1RI 的表达受 IL-7 和 IL-15 的控制。
