Ghimire, Sakhila and Weber, Daniela and Hippe, Katrin and Meedt, Elisabeth and Hoepting, Matthias and Kattner, Anna-Sophia and Hiergeist, Andreas and Gessner, Andre and Matos, Carina and Ghimire, Saroj and Wolff, Daniel and Edinger, Matthias and Hoffmann, Petra and Poeck, Hendrik and Herr, Wolfgang and Holler, Ernst (2021) GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics. FRONTIERS IN IMMUNOLOGY, 12: 753287. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients' gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; CHAIN FATTY-ACIDS; FECAL MICROBIOTA; HUMAN MONOCYTE; MARROW; RECEPTOR; METABOLITES; ACTIVATION; INFLAMMATION; broad-spectrum antibiotics; GPR; Foxp3; GvHD; microbiota; SCFA |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2022 13:15 |
| Last Modified: | 06 Jul 2022 13:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45676 |
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