Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-γ.
Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-γ.
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DOI：
10.1002/eji.201646703
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发表时间：
2017-03
影响因子：
5.4
通讯作者：
van Kooten C
中科院分区：
文献类型：
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作者：
Dixon KO;O'Flynn J;Klar-Mohamad N;Daha MR;van Kooten C
树突状细胞 (DC) 和补体都是先天性和适应性免疫反应的关键成员。最近的实验小鼠模型表明，DC 产生的替代途径 (AP) 成分强烈影响它们激活和调节 T 细胞反应的能力。在本研究中，我们研究了 DC 和耐受性 DC (tolDC) 对 AP 整体调节剂备解素 (fP) 和 H 因子 (fH) 的产生和调节。 fP 和 fH 均由 DC 产生，tolDC 产生的两种 AP 成分水平显着较高。在用 IFN-γ 激活后，两种细胞都会增加 fH 的产生，同时减少 fP 的产生。 IL-27 是 IL-12 家族的成员，可增加 fH，但 fP 的产生不受影响。 DC 和 tolDC 产生的 fP 和 fH 的功能能力通过它们结合 C3b 的能力得到证实。 DC 抑制 fH 产生可增强诱导同种异体 CD4+ T 细胞增殖的能力。相反，抑制 fP 产生会导致同种刺激能力显着降低。总之，本研究表明 DC 产生的 fP 和 fH 会差异调节其免疫原性，并且局部细胞因子环境可以深刻影响 fP 和 fH 的产生。
Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T‐cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs. Upon activation with IFN‐γ both cells increased fH production, while simultaneously decreasing production of fP. IL‐27, a member of the IL‐12 family, increased fH, but production of fP remained unaffected. The functional capacity of fP and fH produced by DCs and tolDCs was confirmed by their ability to bind C3b. Inhibition of fH production by DCs resulted in a greater ability to induce allogenic CD4+ T‐cell proliferation. In contrast, inhibition of fP production led to a significantly reduced allostimulatory capacity. In summary, this study shows that production of fP and fH by DCs, differentially regulates their immunogenicity, and that the local cytokine environment can profoundly affect the production of fP and fH.