TLR9 signaling in fibroblastic reticular cells regulates peritoneal immunity.
TLR9 signaling in fibroblastic reticular cells regulates peritoneal immunity.
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DOI：
10.1172/jci127542
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发表时间：
2019-08
期刊：
影响因子：
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通讯作者：
Li Xu;Yiming Li;Chenxuan Yang;P. Loughran;H. Liao;R. Hoffman;T. Billiar;M. Deng
中科院分区：
文献类型：
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作者：
Li Xu;Yiming Li;Chenxuan Yang;P. Loughran;H. Liao;R. Hoffman;T. Billiar;M. Deng
成纤维细胞网状细胞（FRC）是淋巴器官中的基质细胞亚群和脂肪组织中的脂肪相关淋巴簇（FAT-associated lymphoid clusters，FMCs），在宿主对感染的反应中发挥免疫调节作用，并可用作脓毒症的细胞治疗形式。在此，我们发现了TLR 9在控制基线时和盲肠结扎穿孔（CLP）诱导的脓毒症后腹膜免疫细胞募集和CD 40 C形成中的意想不到的主要作用。TLR 9通过抑制FRC产生趋化因子来调节腹膜免疫。TLR 9缺陷型FRC的连续转移比WT FRC更有效地降低CLP后的死亡率、细菌负荷和全身炎症。重要的是，我们发现TLR 9信号的激活抑制了人脂肪组织来源的FRC产生趋化因子。总之，我们的研究结果表明，TLR 9通过抑制FRC产生趋化因子在调节腹膜免疫中起着关键作用。这些数据形成了一个知识基础，在此基础上设计新的治疗策略，以提高基于FRC的治疗败血症和免疫失调疾病的疗效。
Fibroblastic reticular cells (FRCs), a subpopulation of stromal cells in lymphoid organs and fat-associated lymphoid clusters (FALCs) in adipose tissue, play immune-regulatory roles in the host response to infection and may be useful as a form of cell therapy in sepsis. Here, we found an unexpected major role of TLR9 in controlling peritoneal immune cell recruitment and FALC formation at baseline and after sepsis induced by cecal ligation and puncture (CLP). TLR9 regulated peritoneal immunity via suppression of chemokine production by FRCs. Adoptive transfer of TLR9-deficient FRCs more effectively decreased mortality, bacterial load, and systemic inflammation after CLP than WT FRCs. Importantly, we found that activation of TLR9 signaling suppressed chemokine production by human adipose tissue-derived FRCs. Together, our results indicate that TLR9 plays critical roles in regulating peritoneal immunity via suppression of chemokine production by FRCs. These data form a knowledge basis upon which to design new therapeutic strategies to improve the therapeutic efficacy of FRC-based treatments for sepsis and immune dysregulation diseases.