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Adaptive immunity in obesity and insulin resistance

Abstract

Obesity is the hallmark of the metabolic syndrome and predisposes patients to the development of major chronic metabolic diseases including type 2 diabetes mellitus. Adipose tissue expansion in obesity is characterized by increasing infiltration of proinflammatory immune cells into adipose tissue causing chronic, low-grade inflammation. Phenotypic switching of macrophages is an important mechanism of adipose tissue inflammation, and there is involvement of cells from the adaptive immune system in this process. T-cell phenotype changes and recruitment of B cells and T cells precedes macrophage infiltration. Cytokines and chemokines produced by immune cells influence localized and systemic inflammation, which is a pathogenic link between obesity and insulin resistance. Antigens absorbed from the gut might contribute to T-cell activation and recruitment into visceral adipose tissue in obesity. This Review summarizes, in the context of obesity, the evidence for infiltration of adipose tissue by cells of the adaptive immune system, how adaptive system cells affect innate cell populations and the influence of adaptive immune cells on the development of insulin resistance.

Key Points

  • Inflammation within expanding adipose tissue is a characteristic of obesity

  • Innate immune cells such as M1-type polarized, proinflammatory macrophages are essential components of inflammatory processes that occur in adipose tissue

  • Infiltration of adaptive immune cells precedes the accumulation of macrophages in inflamed adipose tissue

  • Cytokines released from TH1 and TH17 cells could have a role in progressive inflammation and recruitment of macrophages

  • Antigenic material absorbed from the gut could contribute to T-cell activation and recruitment into visceral adipose tissue in obesity, linking nutrition to adipose tissue inflammation

  • Cytokines released from cells of the adaptive immune system could contribute to the insulin resistance that is associated with obesity

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Figure 1: Development of adipose tissue inflammation in obesity.
Figure 2: Gut-derived antigens promote T-cell activation in adipose tissue.

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H. Sell and C. Habich contributed equally to all aspects of this manuscript. J. Eckel contributed to discussions of content, writing and editing of the manuscript before submission.

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Correspondence to Juergen Eckel.

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Sell, H., Habich, C. & Eckel, J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol 8, 709–716 (2012). https://doi.org/10.1038/nrendo.2012.114

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