γδ t cells are reduced and rendered unresponsive by hyperglycemia and chronic tnfα in mouse models of obesity and metabolic diseaseγδt细胞减少,高血糖症和慢性tnfα呈现响应的肥胖和代谢疾病的小鼠模型.pdfVIP

cd T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNFa in Mouse Models of Obesity and Metabolic Disease Kristen R. Taylor, Robyn E. Mills, Anne E. Costanzo, Julie M. Jameson* Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America Abstract Epithelial cells provide an initial line of defense against damage and pathogens in barrier tissues such as the skin; however this balance is disrupted in obesity and metabolic disease. Skin cd T cells recognize epithelial damage, and release cytokines and growth factors that facilitate wound repair. We report here that hyperglycemia results in impaired skin cd T cell proliferation due to altered STAT5 signaling, ultimately resulting in half the number of cd T cells populating the epidermis. Skin cd T cells that overcome this hyperglycemic state are unresponsive to epithelial cell damage due to chronic inflammatory mediators, including TNFa. Cytokine and growth factor production at the site of tissue damage was partially restored by administering neutralizing TNFa antibodies in vivo. Thus, metabolic disease negatively impacts homeostasis and functionality of skin cd T cells, rendering host defense mechanisms vulnerable to injury and infection. Citation: Taylor KR, Mills RE, Costanzo AE, Jameson JM (2010) cd T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNFa in Mouse Models of Obesity and Metabolic Disease. PLoS ONE 5(7): e11422. doi:10.1371/journal.pone.0011422 Editor: Nick Gay, University of Cambridge, United Kingdom Received April 12, 2010; Accepted June 11, 2010; Published July 2, 2010 Copyright: 2010 Taylor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted