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

Christian Perez Shibayama, Cristina Gil Cruz, Hung-Wei Cheng, Lucas Onder, Andrea Printz, Urs Mörbe, Mario Novkovic, Conglei Li, Constantino Lopez-Macias, Matthew B Buechler, Shannon J Turley, Matthias Mack, Charlotte Soneson, Mark D Robinson, Elke Scandella, Jennifer Gommerman & Burkhard Ludewig

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 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.
   
citation Perez Shibayama C, Gil Cruz C, Cheng H W, Onder L, Printz A, Mörbe U, Novkovic M, Li C, Lopez-Macias C, Buechler M B, Turley S J, Mack M, Soneson C, Robinson M D, Scandella E, Gommerman J, Ludewig B. Fibroblastic reticular cells initiate immune responses in visceral adipose tissues and secure peritoneal immunity. Sci Immunol 2018; 3:.
   
type journal paper/review (English)
date of publishing 10-8-2018
journal title Sci Immunol (3/26)
ISSN electronic 2470-9468
PubMed 30097537
DOI 10.1126/sciimmunol.aar4539