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Sci Immunol. 2018 Aug 10;3(26). pii: eaar4539. doi: 10.1126/sciimmunol.aar4539.

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

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Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
Nuffield Department of Immunology, University of Oxford, Oxford, UK.
Department of Cancer Immunology, Genentech Inc., San Francisco, CA 94080, USA.
Department of Internal Medicine II-Nephrology, University Hospital Regensburg, Regensburg, Germany.
Institute of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland.


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.

[Indexed for MEDLINE]

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