Presence, function, and regulation of IL-17F-expressing human CD4+ T cells
Presence, function, and regulation of IL-17F-expressing human CD4+ T cells
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DOI：
10.1002/eji.201948138
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发表时间：
2020-01-16
影响因子：
5.4
通讯作者：
Taams, Leonie S.
中科院分区：
文献类型：
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作者：
Burns, Lachrissa A.;Maroof, Ash;Taams, Leonie S.
促炎细胞因子IL-17 A与炎性关节炎的免疫病理学有关。IL-17 F与IL-17 A具有50%的同源性，最近被认为在炎症中起作用。我们研究了IL-17 F（+）CD 4（+）T细胞的诱导和细胞因子谱，以及IL-17 F如何促进炎症。在用IL-1 β、IL-23、抗CD 3和抗CD 28 mAb培养健康供体CD 4（+）T细胞后，检测到IL-17 A和IL-17 F表达细胞。与IL-17 A（+）IL-17 F（-）CD 4（+）T细胞相比，IL-17 F（+）IL-17 A（-）和IL-17 A（+）IL-17 F（+）CD 4（+）T细胞含有较低比例的表达IL-10和表达GM-CSF的细胞和较高比例的表达IFN-γ的细胞。抗CD 28 mAb的滴定显示，强共刺激增加了IL-17 F（+）IL-17 A（-）和IL-17 A（+）IL-17 F（+）CD 4（+）T细胞频率，而IL-17 A（+）IL-17 F（-）CD 4（+）T细胞频率降低。这部分通过IL-2依赖性机制介导。将IL-17 A、IL-17 F和TNF-α添加到来自患有炎性关节炎的患者的滑膜成纤维细胞中导致IL-6和IL-8的显著产生，IL-17 A和IL-17 F的组合阻断比IL-17 A单独阻断在更大程度上降低了IL-6和IL-8的产生。我们的数据表明，IL-17 A和IL-17 F在T细胞共刺激时受到差异调节，并且IL-17 A和IL-17 F的双重阻断比单独的IL-17 A阻断更有效地减少炎症。
The pro-inflammatory cytokine IL-17A has been implicated in the immunopathology of inflammatory arthritis. IL-17F bears 50% homology to IL-17A and has recently been suggested to play a role in inflammation. We investigated the induction and cytokine profile of IL-17F(+) CD4(+) T cells, and how IL-17F may contribute to inflammation. Upon culture of healthy donor CD4(+) T cells with IL-1 beta, IL-23, anti-CD3, and anti-CD28 mAb, both IL-17A and IL-17F-expressing cells were detected. In comparison to IL-17A(+)IL-17F(-) CD4(+) T cells, IL-17F(+)IL-17A(-) and IL-17A(+)IL-17F(+) CD4(+) T cells contained lower proportions of IL-10-expressing and GM-CSF-expressing cells and higher proportions of IFN-gamma-expressing cells. Titration of anti-CD28 mAb revealed that strong co-stimulation increased IL-17F(+)IL-17A(-) and IL-17A(+)IL-17F(+) CD4(+) T cell frequencies, whereas IL-17A(+)IL-17F(-) CD4(+) T cell frequencies decreased. This was partly mediated via an IL-2-dependent mechanism. Addition of IL-17A, IL-17F, and TNF-alpha to synovial fibroblasts from patients with inflammatory arthritis resulted in significant production of IL-6 and IL-8, which was reduced to a larger extent by combined blockade of IL-17A and IL-17F than blockade of IL-17A alone. Our data indicate that IL-17A and IL-17F are differentially regulated upon T cell co-stimulation, and that dual blockade of IL-17A and IL-17F reduces inflammation more effectively than IL-17A blockade alone.