Research ArticleLYMPHATICS

Fibroblastic reticular cells initiate immune responses in visceral adipose tissues and secure peritoneal immunity

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Science Immunology  10 Aug 2018:
Vol. 3, Issue 26, eaar4539
DOI: 10.1126/sciimmunol.aar4539

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Setting the stage for attack

In classical secondary lymphoid organs (SLOs) such as lymph nodes, tonsils, and Peyer’s patches, it is well established that fibroblastic reticular cells (FRCs) play an integral role in the generation of immune responses. Nonclassical SLOs, including fat-associated lymphoid clusters (FALCs), also play important roles in systemic immunity. However, the role of FRCs in FALCs has not been previously examined. Here, using Ccl19-driven cre to delete MYD88 in FALC-associated FRCs, Perez-Shibayama et al. report that FRCs in FALCs play both organizational and immunomodulatory roles. These studies add to the growing recognition of the importance of stromal cells in shaping immune organs and immune responses.

Abstract

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 Salmonella 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.

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