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

Perez-Shibayama, Christian and Gil-Cruz, Cristina and Cheng, Hung-Wei and Onder, Lucas and Printz, Andrea and Morbe, Urs and Novkovic, Mario and Li, Conglei and Lopez-Macias, Constantino and Buechler, Matthew B. and Turley, Shannon J. and Mack, Matthias and Soneson, Charlotte and Robinson, Mark D. and Scandella, Elke and Gommerman, Jennifer and Ludewig, Burkhard (2018) Fibroblastic reticular cells initiate immune responses in visceral adipose tissues and secure peritoneal immunity. SCIENCE IMMUNOLOGY, 3 (26): eaar4539. ISSN 2470-9468,

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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.

Item Type: Article
Uncontrolled Keywords: FOLLICULAR DENDRITIC CELLS; OMENTAL MILKY SPOTS; LYMPH-NODES; INFLAMMATORY MONOCYTES; CHEMOKINE RECEPTORS; INDUCER CELLS; SALMONELLA; DEFENSE; IGM; MAINTENANCE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Nephrologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Mar 2020 13:17
Last Modified: 05 Mar 2020 13:17
URI: https://pred.uni-regensburg.de/id/eprint/14137

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