Inflammation-induced formation of fat-associated lymphoid clusters

Abstract

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

Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer’s Disease?

“…However, EAE could be induced in mice lacking lymph nodes (Map3k14 aly and LTbR −/− mice), suggesting that secondary lymphoid organs are not necessary for initiation of the disease (Greter et al, 2009). The presence of non-classical lymphoid organs has been reported in certain tissues, notably in the fat (Bénézech et al, 2015; Elewa et al, 2014), and might participate in tissue-specific immune responses (Bénézech et al, 2015). It is possible that the presence of such a system, or other organs (Greter et al, 2009) could take over the role of secondary lymphoid organs in those strains of mice that lack them.…”

Fat-Associated Lymphoid Clusters in Inflammation and Immunity

“…Fat-associated lymphoid clusters are non-classical lymphoid tissues associated to adipocytes in mucosal surfaces, including omental, mesenteric, mediastinal, gonadal, and pericardial fat (19, 24, 25). …”

“…Whereas gonadal AT has as little as 1–2 clusters, the omentum can harbor up to 80 clusters per depot in homeostatic conditions (24). This heterogeneity is also reflected in FALC size, which ranges from 100 to 500 µm in diameter (19).…”

“…For instance, no discernible B and T cell compartmentalization areas are evident. Instead, FALCs from mesenteric AT are composed of a tight cluster of B220 + or IgM + B cells, with variable numbers of CD4 + T cells and CD11b + myeloid cells (19, 24). Both myeloid cell precursors (CD31/ER-MP58 + ) and mature macrophages (F4/80 + ) have been detected in omental FALCs, suggesting that these lymphoid clusters form permissive microenvironments where the former cells can proliferate locally to be a source of free macrophages within the peritoneal cavity (32).…”

Potential of Cells and Cytokines/Chemokines to Regulate Tertiary Lymphoid Structures in Human Diseases

“…CD4+ T helper (Th) cells in a special TLS, which is formed during chronic allergic inflammation in the lung and named inducible bronchus-associated lymphoid tissue (iBALT), show a memory phenotype (39). NKT cells restricted by the antigen-presenting molecule CD1d seem to be required for inducible formation of fat-associated lymphoid clusters, which support and coordinate the activation of innate B cells and T cells during serosal immune responses in the peritoneal cavity (40). …”