Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin
- Author(s)
- Hochheiser, K; Wiede, F; Wagner, T; Freestone, D; Enders, MH; Olshansky, M; Russ, B; Nüssing, 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;
- Journal Title
- Journal of Experimental Medicine
- 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- 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.
- Publisher
- Rockefeller University Press
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 33914023
- Publisher's Version
- https://doi.org/10.1084/jem.20200940
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-05-11 04:12:09
Last Modified: 2021-05-17 11:05:38