Department of Pathology
Amino Acids, Peptides, and Proteins | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Immune System Diseases | Immunity | Immunopathology | Medical Immunology | Pathological Conditions, Signs and Symptoms | Skin and Connective Tissue Diseases
Atopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing gammadelta T (Tgammadelta17) cells, from birth resulted in spontaneous, highly penetrant AD with many of the major hallmarks of human AD. In Tgammadelta17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance of AD induction. Tgammadelta17 cells respond to skin commensal bacteria and the fulminant disease in their absence was driven by skin commensal bacteria dysbiosis. AD in this model was characterized by highly expanded dermal alphabeta T clonotypes that produce the type three cytokines, IL-17 and IL-22. These results demonstrate that neonatal Tgammadelta17 cells are innate skin regulatory T cells that are critical for skin homeostasis, and that IL-17 has dual homeostatic and inflammatory function in the skin.
atopic dermatitis, barrier autoimmunity, immunology, inflammation, interleukin-17, mouse, skin T cells
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DOI of Published Version
Spidale NA, Malhotra N, Frascoli M, Sylvia K, Miu B, Freeman C, Stadinski BD, Huseby E, Kang J. Neonatal-derived IL-17 producing dermal γδ T cells are required to prevent spontaneous atopic dermatitis. Elife. 2020 Feb 17;9:e51188. doi: 10.7554/eLife.51188. PMID: 32065580; PMCID: PMC7025821. Link to article on publisher's site
Spidale NA, Malhotra N, Frascoli M, Sylvia KE, Miu B, Freeman C, Stadinski BD, Huseby E, Kang J. (2020). Neonatal-derived IL-17 producing dermal gammadelta T cells are required to prevent spontaneous atopic dermatitis. Open Access Articles. https://doi.org/10.7554/eLife.51188. Retrieved from https://escholarship.umassmed.edu/oapubs/4154
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