Gammadelta T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNFalpha in mouse models of obesity and metabolic disease.
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 gammadelta T cells recognize epithelial damage, and release cytokines and growth factors that facilitate wound repair. We report here that hyperglycemia results in impaired skin gammadelta T cell proliferation due to altered STAT5 signaling, ultimately resulting in half the number of gammadelta T cells populating the epidermis. Skin gammadelta T cells that overcome this hyperglycemic state are unresponsive to epithelial cell damage due to chronic inflammatory mediators, including TNFalpha. Cytokine and growth factor production at the site of tissue damage was partially restored by administering neutralizing TNFalpha antibodies in vivo. Thus, metabolic disease negatively impacts homeostasis and functionality of skin gammadelta T cells, rendering host defense mechanisms vulnerable to injury and infection.
Taylor
Kristen R
KR
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
Mills
Robyn E
RE
Costanzo
Anne E
AE
Jameson
Julie M
JM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006943:Hyperglycemia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008659:Metabolic Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
D000906:Antibodies; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D014409:Tumor Necrosis Factor-alpha