Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Sci Immunol. 2018 Aug 10;3(26). doi: 10.1126/sciimmunol.aar4539.
Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in nonclassical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). Compared with classical secondary lymphoid organs such as lymph nodes and Peyer's patches, FALCs develop along distinct differentiation trajectories and display a reduced structural complexity. Although it is well established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of classical secondary lymphoid organs, the role of FRCs in FALC-dependent peritoneal immunity remains unclear. Using FRC-specific gene targeting, we found that FRCs play an essential role in FALC-driven immune responses. Specifically, we report that initiation of peritoneal immunity was governed through FRC activation in a myeloid differentiation primary response 88 (MYD88)-dependent manner. FRC-specific ablation of MYD88 blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4 T cell-dependent B-cell activation and IgG class switching. Moreover, containment of infection was compromised in mice lacking MYD88 expression in FRCs, indicating that FRCs in FALCs function as an initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.
体腔的免疫保护依赖于先天免疫和适应性免疫反应在非经典次级淋巴器官（如脂肪相关淋巴簇，FALC）中的快速激活。与淋巴结和派尔集合淋巴结等经典次级淋巴器官相比，FALC 沿着独特的分化轨迹发育，并表现出降低的结构复杂性。尽管成纤维网状细胞（FRC）是经典次级淋巴器官免疫刺激基础设施的一个组成部分已得到充分证实，但 FRC 在 FALC 依赖的腹膜免疫中的作用仍不清楚。使用 FRC 特异性基因靶向，我们发现 FRC 在 FALC 驱动的免疫反应中起关键作用。具体而言，我们报告说，FRC 的激活通过髓样分化初级反应 88（MYD88）依赖性方式来控制腹膜免疫的起始。FRC 特异性 MYD88 缺失阻止了炎症单核细胞向 FALC 的募集以及随后的 CD4 T 细胞依赖性 B 细胞激活和 IgG 类转换。此外，在 FRC 中缺乏 MYD88 表达的小鼠中，感染的控制受到损害，表明 FALC 中的 FRC 作为腹膜腔中保护性免疫反应协调的初始检查点发挥作用。
