Defects in skin gamma delta T cell function contribute to delayed wound repair in rapamycin-treated mice
Graduate School of Biomedical Sciences; Department of Immunology
Medical Subject Headings
Animals; Cell Line; Disease Models, Animal; Epidermis; Immunosuppressive Agents; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Culture Techniques; Protein Kinases; Receptors, Antigen, T-Cell, gamma-delta; Sirolimus; Skin; T-Lymphocyte Subsets; Time Factors; Wound Healing
Life Sciences | Medicine and Health Sciences
Disruptions in the normal program of tissue repair can result in poor wound healing, which perturbs the integrity of barrier tissues such as the skin. Such defects in wound repair occur in transplant recipients treated with the immunosuppressant drug rapamycin (sirolimus). Intraepithelial lymphocytes, such as gammadelta T cells in the skin, mediate tissue repair through the production of cytokines and growth factors. The capacity of skin-resident T cells to function during rapamycin treatment was analyzed in a mouse model of wound repair. Rapamycin treatment renders skin gammadelta T cells unable to proliferate, migrate, and produce normal levels of growth factors. The observed impairment of skin gammadelta T cell function is directly related to the inhibitory action of rapamycin on mammalian target of rapamycin. Skin gammadelta T cells treated with rapamycin are refractory to IL-2 stimulation and attempt to survive in the absence of cytokine and growth factor signaling by undergoing autophagy. Normal wound closure can be restored in rapamycin-treated mice by addition of the skin gammadelta T cell-produced factor, insulin-like growth factor-1. These studies not only reveal that mammalian target of rapamycin is a master regulator of gammadelta T cell function but also provide a novel mechanism for the increased susceptibility to nonhealing wounds that occurs during rapamycin administration.
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Citation: J Immunol. 2008 Sep 15;181(6):3974-83.
Journal of immunology (Baltimore, Md. : 1950)
Mills, Robyn E.; Taylor, Kristen R.; Podshivalova, Katie; McKay, Dianne B.; and Jameson, Julie Marie, "Defects in skin gamma delta T cell function contribute to delayed wound repair in rapamycin-treated mice" (2008). GSBS Student Publications. 1554.