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von Werdt, Diego; Gungor, Bilgi; Barreto de Albuquerque, Juliana; Gruber, Thomas; Zysset, Daniel; Kwong Chung, Cheong K. C.; Corrêa-Ferreira, Antonia; Berchtold, Regina; Page, Nicolas; Schenk, Mirjam; Kehrl, John H.; Merkler, Doron; Imhof, Beat A.; Stein, Jens V.; Abe, Jun; Turchinovich, Gleb; Finke, Daniela; Hayday, Adrian C.; Corazza, Nadia; Mueller, Christoph

Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity

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  • Medientyp: E-Artikel
  • Titel: Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity
  • Beteiligte: von Werdt, Diego; Gungor, Bilgi; Barreto de Albuquerque, Juliana; Gruber, Thomas; Zysset, Daniel; Kwong Chung, Cheong K. C.; Corrêa-Ferreira, Antonia; Berchtold, Regina; Page, Nicolas; Schenk, Mirjam; Kehrl, John H.; Merkler, Doron; Imhof, Beat A.; Stein, Jens V.; Abe, Jun; Turchinovich, Gleb; Finke, Daniela; Hayday, Adrian C.; Corazza, Nadia; Mueller, Christoph
  • Erschienen: Frontiers Media SA, 2023
  • Erschienen in: Frontiers in Immunology
  • Sprache: Nicht zu entscheiden
  • DOI: 10.3389/fimmu.2023.1085895
  • ISSN: 1664-3224
  • Schlagwörter: Immunology ; Immunology and Allergy
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>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 Gα protein subunits. The Rgs family member <jats:italic>Rgs1</jats:italic> is one of the most up-regulated genes in tissue-resident memory (T<jats:sub>RM</jats:sub>) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of <jats:italic>Rgs1</jats:italic> 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 naïve OT-I T cells <jats:italic>in vivo</jats:italic> following intestinal infection with <jats:italic>Listeria monocytogenes</jats:italic>-OVA. In bone marrow chimeras, <jats:italic>Rgs1</jats:italic><jats:sup>-/-</jats:sup> and <jats:italic>Rgs1</jats:italic><jats:sup>+/+</jats:sup> 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 <jats:italic>Listeria monocytogenes</jats:italic>-OVA, however, OT-I <jats:italic>Rgs1</jats:italic><jats:sup>+/+</jats:sup> T cells outnumbered the co-transferred OT-I <jats:italic>Rgs1<jats:sup>-</jats:sup></jats:italic><jats:sup>/-</jats:sup> T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I <jats:italic>Rgs1</jats:italic><jats:sup>-/-</jats:sup> T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I <jats:italic>Rgs1</jats:italic><jats:sup>+/+</jats:sup> T<jats:sub>RM</jats:sub> cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I <jats:italic>Rgs1</jats:italic><jats:sup>-/-</jats:sup> T<jats:sub>RM</jats:sub> cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify <jats:italic>Rgs1</jats:italic> as a critical regulator for the generation and maintenance of tissue-resident CD8<jats:sup>+</jats:sup> T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.</jats:p>
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