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

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 and Mueller, Christoph (2023). Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity. Frontiers in immunology, 14, p. 1085895. Frontiers Research Foundation 10.3389/fimmu.2023.1085895

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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 Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) 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 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 naïve 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 +/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 -/- TRM 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

von Werdt, Diego, Gungor, Bilgi, Barreto de Albuquerque, Juliana, Gruber, Thomas, Zysset, Daniel, Kwong Chung, Cheong Kwet Choy, Corrêa Castro Ferreira, Antonia, Berchtold, Regina, Schenk, Mirjam, Imhof, Beat, Corazza, Nadia, Müller, Christoph (A)


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology




Frontiers Research Foundation




Pubmed Import

Date Deposited:

09 May 2023 09:27

Last Modified:

21 May 2023 02:25

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Uncontrolled Keywords:

T-cell differentiation TRM cells immunosurveillance intestinal listeria monocytogenes infection regulator of G-protein signaling-1




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