%0 Journal Article
%T ¦Ã¦Ä T Cells Are Reduced and Rendered Unresponsive by Hyperglycemia and Chronic TNF¦Á in Mouse Models of Obesity and Metabolic Disease
%A Kristen R. Taylor
%A Robyn E. Mills
%A Anne E. Costanzo
%A Julie M. Jameson
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0011422
%X 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 ¦Ã¦Ä T cells recognize epithelial damage, and release cytokines and growth factors that facilitate wound repair. We report here that hyperglycemia results in impaired skin ¦Ã¦Ä T cell proliferation due to altered STAT5 signaling, ultimately resulting in half the number of ¦Ã¦Ä T cells populating the epidermis. Skin ¦Ã¦Ä T cells that overcome this hyperglycemic state are unresponsive to epithelial cell damage due to chronic inflammatory mediators, including TNF¦Á. Cytokine and growth factor production at the site of tissue damage was partially restored by administering neutralizing TNF¦Á antibodies in vivo. Thus, metabolic disease negatively impacts homeostasis and functionality of skin ¦Ã¦Ä T cells, rendering host defense mechanisms vulnerable to injury and infection.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011422