Type I Interferon Signaling in Dendritic Cells Stimulates the Development of Lymph-Node-Resident T Follicular Helper Cells
Type I Interferon Signaling in Dendritic Cells Stimulates the Development of Lymph-Node-Resident T Follicular Helper Cells
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DOI：
10.1016/j.immuni.2009.07.005
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发表时间：
2009-09-18
期刊：
影响因子：
32.4
通讯作者：
Johansson-Lindbom, Bengt
中科院分区：
文献类型：
--
作者：
Cucak, Helena;Yrlid, Ulf;Johansson-Lindbom, Bengt
滤泡辅助性T细胞（Tfh）代表了最近定义的CD 4（+）T细胞亚群，其特征在于表达趋化因子受体CXCR 5和增强的支持B细胞产生抗体应答的能力。在这里，我们证明了淋巴结驻留的CXCR 5（+）Tfh细胞和肠道归巢整合素α（4）β（7）表达的T辅助细胞在肠道引流肠系膜淋巴结中作为单独的亚群产生。树突状细胞和非造血细胞中的I型干扰素信号传导选择性地刺激Tfh细胞发育，以响应与Toll样受体（TLR）3或TLR 4激动剂结合的抗原。与此一致，树突状细胞产生体内Tfh分化所需的细胞因子IL-6的能力和抗体亲和力成熟在I型干扰素信号传导不存在的情况下都降低。因此，我们的研究结果确定I型干扰素作为一种天然佐剂，选择性地支持淋巴结驻留Tfh细胞的产生。
T follicular helper (Tfh) cells represent a recently defined CD4(+) T cell subset characterized by the expression of the chemokine receptor CXCR5 and an enhanced ability to support B cells to mount antibody responses. Here, we demonstrate that lymph-node-resident CXCR5(+) Tfh cells and gut-homing integrin alpha(4)beta(7)-expressing T helper cells are generate as separate subsets in the gut-draining mesenteric lymph nodes. Type I interferon signaling in dendritic cells and in nonhematopoietic cells selectively stimulates Tfh cell development in response to antigen in conjunction with Toll-like receptor (TLR)3 or TLR4 agonists. Consistent with this, the ability of dendritic cells to produce the cytokine IL-6, required for in vivo Tfh differentiation, and antibody affinity maturation are both reduced in absence of type I interferon signaling. Thus, our results identify type I interferon as a natural adjuvant that selectively supports the generation of lymph node resident Tfh cells.