| First Author | Hochheiser K | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 6 | PubMed ID | 33914023 |
| Mgi Jnum | J:343869 | Mgi Id | MGI:6724848 |
| Doi | 10.1084/jem.20200940 | Citation | Hochheiser K, et al. (2021) Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin. J Exp Med 218(6) |
| abstractText | 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. |
