High Fat Diet-Induced CD8+ T Cells in Adipose Tissue Mediate Macrophages to Sustain Low-Grade Chronic Inflammation.

Abstract

Obesity in the United States and worldwide reached epidemic proportions within the last 20 years. Obesity is a very powerful health determinant or indicator that facilitates the development and progression of several metabolic diseases, insulin resistance, and low-grade chronic inflammation. Low-grade chronic inflammation in adipose tissue (AT) is marked by the accumulation of T cells, macrophages, and other immune cells and increased production of proinflammatory cytokines. During the onset of obesity but before the influx of macrophages, the AT is infiltrated by T cells that are strongly implicated in the initiation of obesity-associated inflammation. In comparing mice fed a high-fat diet (HFD) with those fed a normal diet (ND), we observed in HFD epididymal AT induction and infiltration of activated T cells, an accumulation and polarization of macrophages, and an increase in populations of activated CD4+ T cells and CD8+ T cells that express CXCR3 or killer cell lectin-like receptor subfamily G member 1 (KLRG1). Levels of inflammatory cytokines and leptin and the results of in vitro co-culture experiments revealed interactions among HFD- and ND-induced CD8+ T cells, macrophages, and adipocytes. Our findings suggest that obese tissues activate and induce both CD4+ and CD8+ CD69+ T cells and augment the expression of CXCR3 receptors, which promotes the recruitment and numbers of pro-inflammatory M1 macrophages to maintain low-grade chronic inflammation. The results support the hypothesis that CXCR3-expressing CD8+T cells play an essential role in the initiation and maintenance of adipose tissue inflammation.

• Authors: Sonia Kiran, Vijay Kumar, E Angela Murphy, Reilly T Enos, Udai P Singh
• Journal: Frontiers in immunology (Front Immunol) Vol. 12 Pg. 680944 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 34248964 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Kiran, Kumar, Murphy, Enos and Singh.

Chemical References

• Biomarkers
• Cxcr3 protein, mouse
• Cytokines
• Receptors, CXCR3

Topics

• Adipose Tissue (immunology, metabolism)
• Animals
• Biomarkers
• Body Weight
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cells, Cultured
• Chronic Disease
• Cytokines (metabolism)
• Diet, High-Fat (adverse effects)
• Disease Models, Animal
• Energy Metabolism
• Gene Expression
• Immunophenotyping
• Inflammation (etiology, metabolism, pathology)
• Lymphocyte Count
• Macrophages (immunology, metabolism)
• Male
• Mice
• Receptors, CXCR3 (genetics, metabolism)