含TIR结构域的接头分子诱导干扰素（TRIF）调节肠道中的CXCR5⁺辅助性T细胞。
TIR-Domain-Containing Adapter-Inducing Interferon- (TRIF) Regulates CXCR5+ T helper Cells in the Intestine.
作者信息
Kanagavelu Saravana, Flores Claudia, Hagiwara Shinichiro, Ruiz Jose, Hyun Jinhee, Cho Ei E, Sun Frank, Romero Laura, Shih David Q, Fukata Masayuki
机构信息
Division of Gastroenterology, Department of Medicine, F. Widjaja Foundation, Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA; Division of Infectious Diseases and Immunology, Department of Biomedical Science, Medicine and Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Division of Gastroenterology, Department of Medicine, F. Widjaja Foundation, Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
出版信息
J Clin Cell Immunol. 2016 Oct;7(5). doi: 10.4172/2155-9899.1000458. Epub 2016 Sep 30.
OBJECTIVE
Establishing an effective humoral immunity is an important host defense mechanism in intestinal mucosa. T follicular helper (Tfh) cells are a spectrum of CXCR5 expressing T helper cells that induce antigen-specific B cell differentiation. Because the differentiation of T helper cells is largely regulated by innate immunity, we addressed whether TRIF signaling regulates Tfh cell differentiation and its ability to trigger humoral immune responses in the intestine.
METHOD
CD4CXCR5 T cells, B cells, and plasma cells in the Peyer's patches (PPs) of WT and TRIF-deficient (Trif) mice were analyzed by flow cytometry at the baseline, 9 days post primary infection, and 7 days post-secondary infection with . -specific CD4CXCR5 T cells were generated by co-culturing peritoneal macrophages with splenic naïve T cells in the presence of lysate. WT and Trif mice received CD4CXCR5 T cells isolated either from -primed WT mice or generated . These mice were infected with and followed up to 4 weeks. -specific IgA and IgG were measured in stool and serum samples, respectively.
RESULTS
At baseline, CD4CXCR5 T cell proportion was higher but the proportion of B cells and plasma cells was lower in the PPs of Trif mice compared to WT mice. After infection, the proportion of plasma cells also became higher in the PPs of Trif mice compared to WT mice. Corresponding increase of -specific stool IgA but not serum IgG was found in Trif mice compared to WT mice. Both isolated and generated CD4CXCR5 T cells induced protective immunity against infection.
CONCLUSION
Our results reveal a novel role of TRIF in the regulation of humoral immunity in the intestine that can be utilized as a basis for a unique vaccine strategy.
目的
建立有效的体液免疫是肠道黏膜重要的宿主防御机制。滤泡辅助性T（Tfh）细胞是表达CXCR5的一系列辅助性T细胞，可诱导抗原特异性B细胞分化。由于辅助性T细胞的分化很大程度上受固有免疫调节，我们探讨了TRIF信号是否调节Tfh细胞分化及其在肠道中触发体液免疫反应的能力。
方法
通过流式细胞术分析野生型（WT）和TRIF缺陷型（Trif）小鼠派尔集合淋巴结（PPs）中的CD4⁺CXCR5⁺ T细胞、B细胞和浆细胞，分别在基线、初次感染后9天和再次感染后7天进行检测。用特异性CD4⁺CXCR5⁺ T细胞通过在存在裂解物的情况下将腹膜巨噬细胞与脾幼稚T细胞共培养来产生。WT和Trif小鼠接受从经致敏的WT小鼠分离或产生的CD4⁺CXCR5⁺ T细胞。这些小鼠感染后随访4周。分别在粪便和血清样本中测量特异性IgA和IgG。
结果
在基线时，与WT小鼠相比，Trif小鼠PPs中CD4⁺CXCR5⁺ T细胞比例较高，但B细胞和浆细胞比例较低。感染后，与WT小鼠相比，Trif小鼠PPs中浆细胞比例也更高。与WT小鼠相比，Trif小鼠粪便中特异性IgA相应增加，但血清IgG未增加。分离的和产生的CD4⁺CXCR5⁺ T细胞均诱导针对感染的保护性免疫。
结论
我们的结果揭示了TRIF在调节肠道体液免疫中的新作用，可作为独特疫苗策略的基础。
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