Projects per year
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.
Original language | English |
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Article number | e20200940 |
Number of pages | 21 |
Journal | Journal of Experimental Medicine |
Volume | 218 |
Issue number | 6 |
DOIs | |
Publication status | Published - 29 Apr 2021 |
Projects
- 2 Finished
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Next Generation Cell Therapies for Cancer
Tiganis, T., Huntington, N., Darcy, P., Zhang, Z., Cursons, J. & Vivier, E.
1/12/19 → 31/12/23
Project: Research
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NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
1/01/06 → 31/12/20
Project: Research