Complement component C3 mediates Th1/Th17 polarization in human T-cell activation and cutaneous GVHD.
Complement component C3 mediates Th1/Th17 polarization in human T-cell activation and cutaneous GVHD.
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DOI：
10.1038/bmt.2014.75
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发表时间：
2014-07
影响因子：
4.8
通讯作者：
Afshar-Kharghan, V.
中科院分区：
文献类型：
--
作者：
Ma, Q.;Li, D.;Carreno, R.;Patenia, R.;Tsai, K. Y.;Xydes-Smith, M.;Alousi, A. M.;Champlin, R. E.;Sale, G. E.;Afshar-Kharghan, V.
补体系统已被证明在移植物抗宿主病（GVHD）中调节T细胞活化和同种免疫反应。补体系统中枢成分C3缺失的小鼠GVHD相关死亡率/发病率显著降低，C3调节小鼠GVHD的Th1/Th17极化。为了研究抗补体治疗是否对人类T细胞活化有任何影响，本研究使用了一种候选药物Compstatin来抑制C3活化。我们发现在Compstatin存在下，激活CD4+细胞中产生IFN-γ (Th1)、IL-4 （Th2）、IL-17 （Th17）、IL-2和TNF-α的细胞频率显著降低。在TCR刺激下，comp抑素治疗降低了CD4+和CD8+ T细胞的增殖。然而，Compstatin不影响活化的CD8+ T细胞中IL-2和TNF-α的产生，CD8+ T细胞分化为不同的记忆亚群和效应亚群保持不变。此外，我们检查了皮肤GVHD患者皮肤和嘴唇活检样本中的补体沉积。在鳞状上皮、真皮、血管和受损汗腺中检测到C3沉积，并与腺体损伤和再生有关。我们得出结论，C3介导Th1/Th17极化在人T细胞活化和皮肤GVHD患者中。
The complement system has been shown to regulate T cell activation and alloimmune responses in graft-versus-host disease (GVHD). Mice deficient in the central component of complement system C3 have significantly lower GVHD-related mortality/morbidity and C3 modulates Th1/Th17 polarization in mouse GVHD. To investigate whether anti-complement therapy has any impact on human T cell activation, a drug candidate Compstatin was used to inhibit C3 activation in this study. We found the frequency of IFN-γ (Th1), IL-4 (Th2), IL-17 (Th17), IL-2 and TNF-α producing cells were significantly reduced among activated CD4+ cells in the presence of Compstatin. Compstatin treatment decreased the proliferation of both CD4+ and CD8+ T cells upon TCR stimulation. However, Compstatin does not affect the production of IL-2 and TNF-α in activated CD8+ T cells, and the differentiation of CD8+ T cells into distinct memory and effector subsets remained intact. Furthermore, we examined complement deposition in the skin and lip biopsy samples of patients diagnosed with cutaneous GVHD. C3 deposition was detected in the squamous epithelium and dermis, blood vessels and damaged sweat glands, and associated with gland damage and regeneration. We conclude that C3 mediates Th1/Th17 polarization in human T cell activation and skin GVHD in patients.
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影响因子：
15.9
作者：
Kwan, Wing-Hong;Hashimoto, Daigo;Heeger, Peter S.
通讯作者：
Heeger, Peter S.
影响因子：
20.3
作者：
Nilsson, B;Larsson, R;Lambris, JD
通讯作者：
Lambris, JD
影响因子：
3.6
作者：
Niculescu, F;Niculescu, T;Via, CS
通讯作者：
Via, CS
DOI：
10.1097/cji.0b013e3181fb0486
发表时间：
2010-11
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Li D;Li Y;Hernandez JA;Patenia R;Kim TK;Khalili J;Dougherty MC;Hanley PJ;Bollard CM;Komanduri KV;Hwu P;Champlin RE;Radvanyi LG;Molldrem JJ;Ma Q
通讯作者：
Ma Q
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A