Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages
Top Cited Papers
Open Access
- 18 February 2013
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 210 (3), 535-549
- https://doi.org/10.1084/jem.20121964
Abstract
Eosinophils in visceral adipose tissue (VAT) have been implicated in metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence of eosinophils can lead to adiposity and systemic insulin resistance in experimental animals, but what maintains eosinophils in adipose tissue is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation and results in increased adiposity and insulin resistance when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) are resident in VAT and are the major source of IL-5 and IL-13, which promote the accumulation of eosinophils and AAM. Deletion of ILC2s causes significant reductions in VAT eosinophils and AAMs, and also impairs the expansion of VAT eosinophils after infection with Nippostrongylus brasiliensis , an intestinal parasite associated with increased adipose ILC2 cytokine production and enhanced insulin sensitivity. Further, IL-33, a cytokine previously shown to promote cytokine production by ILC2s, leads to rapid ILC2-dependent increases in VAT eosinophils and AAMs. Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation.Keywords
This publication has 56 references indexed in Scilit:
- The Transcription Factor GATA-3 Controls Cell Fate and Maintenance of Type 2 Innate Lymphoid CellsImmunity, 2012
- An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infectionNature Medicine, 2012
- Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunityNature Immunology, 2011
- Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesisNature, 2011
- Macrophage-mediated inflammation in metabolic diseaseNature Reviews Immunology, 2011
- Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunityNature Immunology, 2011
- Nuocytes represent a new innate effector leukocyte that mediates type-2 immunityNature, 2010
- Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parametersNature Medicine, 2009
- Adipocyte-Derived Th2 Cytokines and Myeloid PPARδ Regulate Macrophage Polarization and Insulin SensitivityCell Metabolism, 2008
- Chitin induces accumulation in tissue of innate immune cells associated with allergyNature, 2007