Santarlasci Veronica, Maggi Laura, Capone Manuela, Frosali Francesca, Querci Valentina, De Palma Raffaele, Liotta Francesco, Cosmi Lorenzo, Maggi Enrico, Romagnani Sergio, Annunziato Francesco
Centre of Excellence DENOthe, University of Florence, Florence, Italy.
Eur J Immunol. 2009 Jan;39(1):207-15. doi: 10.1002/eji.200838748.
Human Th17 clones and circulating Th17 cells showed lower susceptibility to the anti-proliferative effect of TGF-beta than Th1 and Th2 clones or circulating Th1-oriented T cells, respectively. Accordingly, human Th17 cells exhibited lower expression of clusterin, and higher Bcl-2 expression and reduced apoptosis in the presence of TGF-beta, in comparison with Th1 cells. Umbilical cord blood naïve CD161(+)CD4(+) T cells, which contain the precursors of human Th17 cells, differentiated into IL-17A-producing cells only in response to IL-1beta plus IL-23, even in serum-free cultures. TGF-beta had no effect on constitutive RORgamma t expression by umbilical cord blood CD161(+) T cells but it increased the relative proportions of CD161(+) T cells differentiating into Th17 cells in response to IL-1beta plus IL-23, whereas under the same conditions it inhibited both T-bet expression and Th1 development. These data suggest that TGF-beta is not critical for the differentiation of human Th17 cells, but indirectly favors their expansion because Th17 cells are poorly susceptible to its suppressive effects.
与Th1和Th2克隆细胞或循环中以Th1为主的T细胞相比，人Th17克隆细胞和循环Th17细胞对转化生长因子-β（TGF-β）的抗增殖作用敏感性较低。因此，与Th1细胞相比，人Th17细胞在TGF-β存在的情况下，簇集蛋白表达较低，Bcl-2表达较高，凋亡减少。脐带血初始CD161(+)CD4(+) T细胞包含人Th17细胞的前体，即使在无血清培养条件下，也仅在白细胞介素-1β（IL-1β）加白细胞介素-23（IL-23）的刺激下分化为产生白细胞介素-17A（IL-17A）的细胞。TGF-β对脐带血CD161(+) T细胞组成型维甲酸相关孤儿受体γt（RORγt）的表达没有影响，但它增加了在IL-1β加IL-23刺激下分化为Th17细胞的CD161(+) T细胞的相对比例，而在相同条件下，它抑制T细胞转录因子（T-bet）的表达和Th1的发育。这些数据表明，TGF-β对人Th17细胞的分化并不关键，但由于Th17细胞对其抑制作用敏感性较差，它间接促进了Th17细胞的扩增。
