Dendritic Cells in Subcutaneous and Epicardial Adipose Tissue of Subjects with Type 2 Diabetes, Obesity, and Coronary Artery Disease
Language English Country United States Media electronic-ecollection
Document type Journal Article
PubMed
31210749
PubMed Central
PMC6532274
DOI
10.1155/2019/5481725
Knihovny.cz E-resources
- MeSH
- Dendritic Cells metabolism MeSH
- Diabetes Mellitus, Type 2 immunology metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Coronary Artery Disease immunology metabolism MeSH
- Obesity immunology metabolism MeSH
- Pericardium immunology metabolism MeSH
- Subcutaneous Fat immunology metabolism MeSH
- Aged MeSH
- Adipose Tissue immunology metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n = 12) and without (non-T2DM, n = 17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6 ± 0.7 vs. 5.8 ± 0.2 mmol/l, p < 0.001) and glycated hemoglobin (52.0 ± 3.4 vs. 36.9 ± 1.0 mmol/mol, p < 0.001) and tended to have more pronounced inflammation (hsCRP: 9.8 ± 3.1 vs. 5.1 ± 1.9 mg/ml, p = 0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57 ± 0.65 vs. 4.45 ± 1.56% for T2DM vs. non-T2DM, p = 0.041) with a similar, albeit insignificant, trend in EAT (0.996 ± 0.33 vs. 2.46 ± 0.78% for T2DM vs. non-T2DM, p = 0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5 ± 2.0 vs. 4.6 ± 1.9% of DC cells, p = 0.005) and EAT (29.1 ± 8.7 vs. 8.4 ± 2.4% of DC, p = 0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1 ± 8.7 vs. 13.5 ± 2.0% of DC, p = 0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.
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Collin M., Bigley V. Human dendritic cell subsets: an update. Immunology. 2018;154(1):3–20. doi: 10.1111/imm.12888. PubMed DOI PMC
Sundara Rajan S., Longhi M. P. Dendritic cells and adipose tissue. Immunology. 2016;149(4):353–361. doi: 10.1111/imm.12653. PubMed DOI PMC
Cools N., Ponsaerts P., van Tendeloo V. F. I., Berneman Z. N. Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. Journal of Leukocyte Biology. 2007;82(6):1365–1374. doi: 10.1189/jlb.0307166. PubMed DOI
Tamura T., Tailor P., Yamaoka K., et al. IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. Journal of Immunology. 2005;174(5):2573–2581. doi: 10.4049/jimmunol.174.5.2573. PubMed DOI
Gilliet M., Cao W., Liu Y. J. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nature Reviews Immunology. 2008;8(8):594–606. doi: 10.1038/nri2358. PubMed DOI
Merad M., Sathe P., Helft J., Miller J., Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annual Review of Immunology. 2013;31(1):563–604. doi: 10.1146/annurev-immunol-020711-074950. PubMed DOI PMC
Chung C. Y. J., Ysebaert D., Berneman Z. N., Cools N. Dendritic cells: cellular mediators for immunological tolerance. Clinical & Developmental Immunology. 2013;2013, article 972865:8. doi: 10.1155/2013/972865. PubMed DOI PMC
Murdolo G., Smith U. The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis. Nutrition, Metabolism, and Cardiovascular Diseases. 2006;16(Supplement 1):S35–S38. doi: 10.1016/j.numecd.2005.10.016. PubMed DOI
Macdougall C. E., Wood E. G., Loschko J., et al. Visceral adipose tissue immune homeostasis is regulated by the crosstalk between adipocytes and dendritic cell subsets. Cell Metabolism. 2018;27(3):588–601.e4. doi: 10.1016/j.cmet.2018.02.007. PubMed DOI PMC
Bertola A., Ciucci T., Rousseau D., et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes. 2012;61(9):2238–2247. doi: 10.2337/db11-1274. PubMed DOI PMC
Chen Y., Tian J., Tian X., et al. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS One. 2014;9(3, article e92450) doi: 10.1371/journal.pone.0092450. PubMed DOI PMC
Stefanovic-Racic M., Yang X., Turner M. S., et al. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes. 2012;61(9):2330–2339. doi: 10.2337/db11-1523. PubMed DOI PMC
Cho K. W., Zamarron B. F., Muir L. A., et al. Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance. Journal of Immunology. 2016;197(9):3650–3661. doi: 10.4049/jimmunol.1600820. PubMed DOI PMC
Salazar J., Luzardo E., Mejías J. C., et al. Epicardial fat: physiological, pathological, and therapeutic implications. Cardiology Research and Practice. 2016;2016:15. doi: 10.1155/2016/1291537.1291537 PubMed DOI PMC
Horckmans M., Bianchini M., Santovito D., et al. Pericardial adipose tissue regulates granulopoiesis, fibrosis, and cardiac function after myocardial infarction. Circulation. 2018;137(9):948–960. doi: 10.1161/CIRCULATIONAHA.117.028833. PubMed DOI
Ghosh A. R., Bhattacharya R., Bhattacharya S., et al. Adipose recruitment and activation of plasmacytoid dendritic cells fuel metaflammation. Diabetes. 2016;65(11):3440–3452. doi: 10.2337/db16-0331. PubMed DOI
Hannibal T. D., Schmidt-Christensen A., Nilsson J., Fransén-Pettersson N., Hansen L., Holmberg D. Deficiency in plasmacytoid dendritic cells and type I interferon signalling prevents diet-induced obesity and insulin resistance in mice. Diabetologia. 2017;60(10):2033–2041. doi: 10.1007/s00125-017-4341-0. PubMed DOI PMC
Henrichot E., Juge-Aubry C. E., Pernin A.`., et al. Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis? Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25(12):2594–2599. doi: 10.1161/01.ATV.0000188508.40052.35. PubMed DOI
Iacobellis G., Corradi D., Sharma A. M. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nature Clinical Practice Cardiovascular Medicine. 2005;2(10):536–543. doi: 10.1038/ncpcardio0319. PubMed DOI
Hirata Y., Kurobe H., Akaike M., et al. Enhanced inflammation in epicardial fat in patients with coronary artery disease. International Heart Journal. 2011;52(3):139–142. doi: 10.1536/ihj.52.139. PubMed DOI
McAninch E. A., Fonseca T. L., Poggioli R., et al. Epicardial adipose tissue has a unique transcriptome modified in severe coronary artery disease. Obesity. 2015;23(6):1267–1278. doi: 10.1002/oby.21059. PubMed DOI PMC
Vianello E., Dozio E., Arnaboldi F., et al. Epicardial adipocyte hypertrophy: association with M1-polarization and toll-like receptor pathways in coronary artery disease patients. Nutrition, Metabolism, and Cardiovascular Diseases. 2016;26(3):246–253. doi: 10.1016/j.numecd.2015.12.005. PubMed DOI
Mazurek T., Zhang L. F., Zalewski A., et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108(20):2460–2466. doi: 10.1161/01.CIR.0000099542.57313.C5. PubMed DOI
Qiu T., Li M., Tanner M. A., et al. Depletion of dendritic cells in perivascular adipose tissue improves arterial relaxation responses in type 2 diabetic mice. Metabolism. 2018;85:76–89. doi: 10.1016/j.metabol.2018.03.002. PubMed DOI PMC
Koivisto V. A., Pelkonen R., Cantell K. Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes. 1989;38(5):641–647. doi: 10.2337/diab.38.5.641. PubMed DOI
Braun D., Caramalho I., Demengeot J. IFN-α/β enhances BCR-dependent B cell responses. International Immunology. 2002;14(4):411–419. doi: 10.1093/intimm/14.4.411. PubMed DOI
Bratke K., Klein C., Kuepper M., Lommatzsch M., Virchow J. C. Differential development of plasmacytoid dendritic cells in Th1- and Th2-like cytokine milieus. Allergy. 2011;66(3):386–395. doi: 10.1111/j.1398-9995.2010.02497.x. PubMed DOI
Alsharifi M., Lobigs M., Regner M., Lee E., Koskinen A., Mullbacher A. Type I interferons trigger systemic, partial lymphocyte activation in response to viral infection. Journal of Immunology. 2005;175(7):4635–4640. doi: 10.4049/jimmunol.175.7.4635. PubMed DOI
Camarena V., Sant D., Mohseni M., et al. Novel atherogenic pathways from the differential transcriptome analysis of diabetic epicardial adipose tissue. Nutrition, Metabolism and Cardiovascular Diseases. 2017;27(8):739–750. doi: 10.1016/j.numecd.2017.05.010. PubMed DOI PMC
Gaborit B., Venteclef N., Ancel P., et al. Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. Cardiovascular Research. 2015;108(1):62–73. doi: 10.1093/cvr/cvv208. PubMed DOI