Carolan Eirin, Tobin Laura M, Mangan Bozgana A, Corrigan Michelle, Gaoatswe Gadinthsware, Byrne Greg, Geoghegan Justin, Cody Declan, O'Connell Jean, Winter Desmond C, Doherty Derek G, Lynch Lydia, O'Shea Donal, Hogan Andrew E
Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland; National Children's Research Centre, Crumlin Children's Hospital, Dublin 12, Ireland;
Obesity Immunology Research, St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland;
J Immunol. 2015 Jun 15;194(12):5775-80. doi: 10.4049/jimmunol.1402945. Epub 2015 May 15.
Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance. MAIT cells were enriched in adipose tissue (AT) compared with blood. AT MAIT cells, but not circulating MAIT cells, were capable of producing IL-10. In AT from obese subjects, MAIT cells were depleted, were less likely to produce IL-10, and more frequently produced IL-17. Finally, we show that IL-17(+) MAIT cells are also increased in childhood obesity, and altered MAIT cell frequencies in obese children are positively associated with insulin resistance. These data indicate that MAIT cells are enriched in human AT and display an IL-17(+) phenotype in both obese adults and children, correlating with levels of insulin resistance. The alterations in MAIT cells may be contributing to obesity-related sterile inflammation and insulin resistance.
黏膜相关恒定T（MAIT）细胞是先天性主要组织相容性复合体（MHC）非限制性细胞，可通过快速产生细胞因子来调节炎症反应。在本文中，我们发现肥胖成年人的循环MAIT细胞减少，且这种减少与糖尿病状态相关。体外刺激时，循环MAIT细胞更频繁地产生白细胞介素-17（IL-17），这是一种与胰岛素抵抗有关的细胞因子。与血液相比，脂肪组织（AT）中的MAIT细胞更为富集。AT中的MAIT细胞能够产生IL-10，但循环MAIT细胞则不能。在肥胖受试者的AT中，MAIT细胞减少，产生IL-10的可能性降低，而产生IL-17的频率增加。最后，我们发现儿童肥胖时IL-17(+) MAIT细胞也会增加，肥胖儿童中MAIT细胞频率的改变与胰岛素抵抗呈正相关。这些数据表明，MAIT细胞在人类AT中富集，在肥胖的成年人和儿童中均表现出IL-17(+)表型，与胰岛素抵抗水平相关。MAIT细胞的改变可能导致了与肥胖相关的无菌性炎症和胰岛素抵抗。
