| First Author | von Werdt D | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1085895 | PubMed ID | 37153600 |
| Mgi Jnum | J:340990 | Mgi Id | MGI:7481496 |
| Doi | 10.3389/fimmu.2023.1085895 | Citation | von Werdt D, et al. (2023) Regulator of G-protein signaling 1 critically supports CD8(+) T(RM) cell-mediated intestinal immunity. Front Immunol 14:1085895 |
| abstractText | Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Galpha protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (T(RM)) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Galphaq, and Galphai protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naive OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1 (-/-) and Rgs1 (+/+) T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1 (+/+) T cells outnumbered the co-transferred OT-I Rgs1(-) (/-) T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1 (-/-) T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1 (+/+) T(RM) cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 (-/-) T(RM) cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8(+) T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens. |
