Inflammation-induced formation of fat-associated lymphoid clusters

Cécile Bénézech, Nguyet-Thin Luu, Jennifer A Walker, Andrei A Kruglov, Yunhua Loo, Kyoko Nakamura, Yang Zhang, Saba Nayar, Lucy H Jones, Adriana Flores-Langarica, Alistair McIntosh, Jennifer Marshall, Francesca Barone, Gurdyal Besra, Katherine Miles, Judith E Allen, Mohini Gray, George Kollias, Adam F Cunningham, David R WithersKai Michael Toellner, Nick D Jones, Marc Veldhoen, Sergei A Nedospasov, Andrew N J McKenzie, Jorge H Caamaño

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Abstract

Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses.

Original languageEnglish
Pages (from-to)819-828
Number of pages10
JournalNature Immunology
Volume16
Issue number8
Early online date29 Jun 2015
DOIs
Publication statusPublished - Aug 2015

Keywords

  • Lymphoid organs
  • Adipose Tissue
  • Inflammation
  • Immune response
  • iNKT cells
  • TNF
  • IL-13
  • Peritoneum

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