Altered CD4+ T cell and cytokine levels in peripheral blood and skin samples from systemic sclerosis patients and IL-35 in CD4+ T cell growth
Altered CD4+ T cell and cytokine levels in peripheral blood and skin samples from systemic sclerosis patients and IL-35 in CD4+ T cell growth
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系统性硬化症患者外周血和皮肤样本中 CD4 T 细胞和细胞因子水平的改变以及 CD4 T 细胞生长中 IL35 的改变
DOI：
10.1093/rheumatology/keab359
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发表时间：
2021-04-20
期刊：
影响因子：
5.5
通讯作者：
Wei，Wanling
中科院分区：
文献类型：
--
作者：
Yang，Chenxi;Lei，Ling;Wei，Wanling
目的探讨白介素35(IL-35)对系统性硬化症患者外周血中CD4+T淋巴细胞及人皮肤成纤维细胞(HSF)活性和细胞因子水平的影响。方法收集41例系统性硬化症患者和39例健康体检者的外周血和皮肤活检标本，检测CD4+T淋巴细胞和IL-35相关因子水平。结果患者外周血中Th1/Th2细胞比例低于对照组(P<； )，Th17/Treg细胞比例高于对照组(P<；p0.05)。IL-35、IL-17A水平高于对照组，干扰素-γ、IL-10、转化生长因子-β水平低于对照组。IL-17A、叉头盒P3、转化生长因子-β1、I型胶原(COL-1)、磷酸化(P)信号转导和转录激活因子(STAT)1、p-STAT4在皮肤组织中的表达均高于对照组(P<； )。细胞培养上清液中IL-6水平较高，而IL-10水平较低。α-平滑肌肌动蛋白(α-SMA)、COL-1蛋白和Ki67阳性细胞均高于对照组。与对照组相比，重组人IL-35可抑制CD4+T淋巴细胞+HSFs的增殖(P<； 0.001)，增加IL-10，减少IL-17A、α-SMA和COL-1的分泌。结论IL-35对 +T淋巴细胞的增殖具有抑制作用，但可能通过激活STAT1信号通路，促进Th1细胞的增殖和胶原蛋白的表达，从而诱导其分化。
ObjectiveThis study explored the role of IL-35 in CD4+T lymphocyte and human skin fibroblast (HSF) activity and cytokine levels in systemic sclerosis.MethodsBlood and skin biopsies were collected from 41 patients and 39 healthy controls to assess CD4+T lymphocytes and IL-35-related factors. CD4+T lymphocytes were co-cultured with HSFs, recombinant human IL-35 and IL-35 mAb to evaluate the cell viability, activation of CD4+T lymphocytes and HSF cells.ResultsThe proportion of blood Th1/Th2 was lower and Th17/Treg was higher in patients than in controls (P< 0.05). IL-35 and IL-17A levels were higher and IFN-γ, IL-10 and TGF-β levels were lower in patients than in controls. IL-17A, forkhead box P3, TGF-β1 and collagen type I (COL-1) mRNA and phospho (p)-signal transducer and activator of transcription (STAT) 1 and p-STAT4 were higher in skin tissues from patients than in those from controls (P< 0.05). IL-6 levels were higher, whereas IL-10 levels were lower in cell culture supernatants. α-Smooth muscle actin (α-SMA) and COL-1 proteins and Ki67 positivity were higher in CD4+T + HSF cells from patients than in those from controls. Recombinant human IL-35 treatment inhibited proliferation (P< 0.001), but increased IL-10 and decreased IL-17A, α-SMA and COL-1 secretion into the conditioned medium of CD4+T lymphocytes + HSFs from patients compared with those from controls. IL-35 mAb blocked the effects of IL-35 in CD4+T + HSF cells (P< 0.05).ConclusionsIL-35 plays an inhibitory role in CD4+T lymphocyte proliferation but induces Treg cell differentiation by STAT1 signalling activation, HSF proliferation and collagen expression in systemic sclerosis.