Journal article

Ptpn2 and KLRG1 regulate the generation and in skin

Katharina Hochheiser, Florian Wiede, Teagan Wagner, David Freestone, Matthias H Enders, Moshe Olshansky, Brendan Russ, Simone Nussing, Emma Bawden, Asolina Braun, Annabell Bachem, Elise Gressier, Robyn McConville, Simone L Park, Claerwen M Jones, Gayle M Davey, David E Gyorki, David Tscharke, Ian A Parish, Stephen Turner Show all

JOURNAL OF EXPERIMENTAL MEDICINE | ROCKEFELLER UNIV PRESS | Published : 2021

Abstract

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- ce..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by German Research Council


Awarded by Leukemia and Lymphoma Society


Funding Acknowledgements

This study was supported by the National Health and Medical Research Council of Australia (grant APP1084805 to T. Gebhardt; grant APP1059514 to T. Gebhardt, D. Tscharke, and S. Bedoui; and grant APP1184615 to T. Tiganis). K. Hochheiser was supported by the German Research Council (grant HO 5417/1-1) and is a Rhian and Paul Brazis Fellow in Translational Melanoma Immunology administered by the Peter MacCallum Cancer Foundation. T. Gebhardt is a Senior Biomedical Research Fellow supported by the Sylvia and Charles Viertel Charitable Foundation. T. Tiganis is a National Health and Medical Research Council of Australia Principal Research Fellow (APP1103037). S.L. Park was supported by an Elizabeth & Vernon Puzey postgraduate scholarship and a Cancer Council Victoria postdoctoral fellowship. M.J. Herold is supported by the National Health and Medical Research Council of Australia (grants APP1186575, APP1159658, and APP1156095) and the Leukemia and Lymphoma Society (grant LLS SCOR 7001-13).