Dataset Information

G?_s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

ABSTRACT: Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of ?₂-integrins. G?_s-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of ?₂-integrins-we show that the G?_s-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E₂, PGD₂, and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8⁺ T cells in a dose-dependent manner. In contrast, sleep, a natural condition of low levels of G?_s-coupled receptor agonists, up-regulates integrin activation compared with nocturnal wakefulness, a mechanism possibly underlying some of the immune-supportive effects of sleep. The findings are also relevant for several pathologies associated with increased levels of G?_s-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).

SUBMITTER: Dimitrov S

PROVIDER: S-EPMC6400544 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gαs-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

Dimitrov Stoyan S Lange Tanja T Gouttefangeas Cécile C Jensen Anja T R ATR Szczepanski Michael M Lehnnolz Jannik J Soekadar Surjo S Rammensee Hans-Georg HG Born Jan J Besedovsky Luciana L

The Journal of experimental medicine 20190212 3

Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of β2-integrins. Gαs-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of β2-integrins-we show that the Gα<sub ...[more]

PMID: 30755455

Similar Datasets

Project description:Background & aimsProliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-protein-coupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis.MethodsIntestinal tissues from control (Gnaqflox/floxGna11+/+ ), Int-Gq knock-out (KO) (VilCre+/-Gnaqflox/floxGna11+/+ ), G11 KO (Gnaqflox/floxGna11-/- ), and Int-Gq/G11 double knock-out (DKO) (VilCre+/-Gnaqflox/floxGna11-/- ) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry. The effect of Gαq/11-mediated signaling was studied in the cell lineage, proliferation, and apoptosis. Dextran sodium sulfate (DSS) colitis was induced to study the role of Gαq/11 in colon.ResultsPaneth cells were enlarged, increased in number, and mislocalized in Int-Gq/G11 DKO small intestine. Paneth cells also reacted with PAS and Muc2 antibody, indicating an intermediate character of Paneth and goblet cells. The nuclear β-catenin, T-cell factor 1, and Sox9 expression were reduced severely in the crypt base of Int-Gq/G11 DKO intestine. Proliferation was activated in the crypt base and apoptosis was enhanced along the crypt. Int-Gq/G11 DKO mice were susceptible to DSS colitis. Proliferation was inhibited in the crypt of unaffected and regenerative areas. Cystic crypts, periodic acid-Schiff-positive cells, and Muc2-positive cells were unusually observed in the ulcerative region.ConclusionsThe Gαq/11-mediated pathway plays a pivotal role in the preservation of intestinal homeostasis, especially in Paneth cell maturation and positioning. Wnt/β-catenin signaling was reduced significantly in the crypt base in Gαq/G11-deficient mice, resulting in the defective maturation of Paneth cells, induction of differentiation toward goblet cells, and susceptibility to DSS colitis.

Dataset Information

G?_s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

Publications

Gα<sub>s</sub>-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

G?s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

Publications

Gα<sub>s</sub>-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

G?_s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.