Journal
MEDIATORS OF INFLAMMATION
Volume 2019, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2019/1648614
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Funding
- NIH/NCI [CA148772]
- U.S. Department of Veterans Affairs Merit Awards [BX002277, BX000333]
- Cell Evaluation & Therapy Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]
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Chronic inflammation is evident in the adipose tissue and periphery of patients with obesity, as well as mouse models of obesity. T cell subsets in obese adipose tissue are skewed towards Th1- and Th17-associated phenotypes and their secreted cytokines contribute to obesity-associated inflammation. Our lab recently identified a novel, myeloid-derived CD45(+)DDR2(+) cell subset that modulates T cell activity. The current study sought to determine how these myeloid-derived CD45(+)DDR2(+) cells are altered in the adipose tissue and peripheral blood of preobese mice and how this population modulates T cell activity. C57BL/6 mice were fed with a diet high in milkfat (60%kcal, HFD) ad libitum until a 20% increase in total body weight was reached, and myeloid-derived CD45(+)DDR2(+) cells and CD4(+) T cells in visceral adipose tissue (VAT), mammary gland-associated adipose tissue (MGAT), and peripheral blood (PB) were phenotypically analyzed. Also analyzed was whether mediators from MGAT-primed myeloid-derived CD45(+)DDR2(+) cells stimulate normal CD4(+) T cell cytokine production. A higher percentage of myeloid-derived CD45(+)DDR2(+) cells expressed the activation markers MHC II and CD80 in both VAT and MGAT of preobese mice. CD4(+) T cells were preferentially skewed towards Th1- and Th17-associated phenotypes in the adipose tissue and periphery of preobese mice. In vitro, MGAT from HFD-fed mice triggered myeloid-derived CD45(+)DDR2(+) cells to induce CD4(+) T cell IFN- and TNF- production. Taken together, this study shows that myeloid-derived CD45(+)DDR2(+) cells express markers of immune activation and suggests that they play an immune modulatory role in the adipose tissue of preobese mice.
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