Visceral Adipose Tissue Immune Homeostasis Is Regulated by the Crosstalk between Adipocytes and Dendritic Cell Subsets

Publication date: 6 March 2018
Source:Cell Metabolism, Volume 27, Issue 3
Author(s): Claire E. Macdougall, Elizabeth G. Wood, Jakob Loschko, Valeria Scagliotti, Féaron C. Cassidy, Mark E. Robinson, Niklas Feldhahn, Leandro Castellano, Mathieu-Benoit Voisin, Federica Marelli-Berg, Carles Gaston-Massuet, Marika Charalambous, M. Paula Longhi
Visceral adipose tissue (VAT) has multiple roles in orchestrating whole-body energy homeostasis. In addition, VAT is now considered an immune site harboring an array of innate and adaptive immune cells with a direct role in immune surveillance and host defense. We report that conventional dendritic cells (cDCs) in VAT acquire a tolerogenic phenotype through upregulation of pathways involved in adipocyte differentiation. While activation of the Wnt/β-catenin pathway in cDC1 DCs induces IL-10 production, upregulation of the PPARγ pathway in cDC2 DCs directly suppresses their activation. Combined, they promote an anti-inflammatory milieu in vivo delaying the onset of obesity-induced chronic inflammation and insulin resistance. Under long-term over-nutrition, changes in adipocyte biology curtail β-catenin and PPARγ activation, contributing to VAT inflammation.

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Teaser

Macdougall et al. report key mechanisms that control the immune function of conventional dendritic cells in visceral adipose tissue. The upregulation of adipocyte-related pathways in conventional dendritic cells promotes an anti-inflammatory phenotype in visceral adipose tissue under homeostatic conditions and delays the onset of obesity-induced inflammation and insulin resistance.


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