Sir Peter MacCallum Department of Oncology - Research Publications

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Author: Bedoui, Sammy × Author: Gressier, Elise × Author: Bachem, Annabell × Type: Journal Article ×

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    Ptpn2 and KLRG1 regulate the generation and in skin
    Hochheiser, K ; Wiede, F ; Wagner, T ; Freestone, D ; Enders, MH ; Olshansky, M ; Russ, B ; Nussing, S ; Bawden, E ; Braun, A ; Bachem, A ; Gressier, E ; McConville, R ; Park, SL ; Jones, CM ; Davey, GM ; Gyorki, DE ; Tscharke, D ; Parish, IA ; Turner, S ; Herold, MJ ; Tiganis, T ; Bedoui, S ; Gebhardt, T (ROCKEFELLER UNIV PRESS, 2021-06-07)
    Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of TRM cells in skin. Ptpn2-deficient CD8+ T cells displayed a marked defect in generating CD69+ CD103+ TRM cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1- memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede TRM cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1- cells restored TRM generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream TRM cell differentiation. Importantly, Ptpn2-deficient TRM cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal TRM cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.