Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.680944
Keywords
obesity; inflammation; chemokine; CD8(+) T cells; macrophages
Categories
Funding
- NIAID [R01 AI140405]
- Intramural Research Program at UTHSC in Memphis, TN
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Obesity is a powerful health indicator that leads to metabolic diseases, insulin resistance, and low-grade chronic inflammation. Research has shown that obese tissues activate and induce CD4(+) and CD8(+) CD69(+) T cells, increase the expression of CXCR3 receptors, and promote recruitment and accumulation of pro-inflammatory M1 macrophages to maintain low-grade chronic inflammation.
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.
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