1. Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule.
- Author
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Ben Nasr M, Usuelli V, Dellepiane S, Seelam AJ, Fiorentino TV, D'Addio F, Fiorina E, Xu C, Xie Y, Balasubramanian HB, Castillo-Leon E, Loreggian L, Maestroni A, Assi E, Loretelli C, Abdelsalam A, El Essawy B, Uccella S, Pastore I, Lunati ME, Sabiu G, Petrazzuolo A, Ducci G, Sacco E, Centofanti L, Venturini M, Mazzucchelli S, Mattinzoli D, Ikehata M, Castellano G, Visner G, Kaifeng L, Lee KM, Wang Z, Corradi D, La Rosa S, Danese S, Yang J, Markmann JF, Zuccotti GV, Abdi R, Folli F, and Fiorina P
- Subjects
- Animals, Mice, T-Lymphocytes immunology, T-Lymphocytes metabolism, Male, Heart Transplantation, Mice, Inbred BALB C, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes immunology, Graft Survival immunology, Glucagon-Like Peptide-1 Receptor metabolism, Mice, Inbred C57BL, Islets of Langerhans Transplantation
- Abstract
Glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of glucose metabolism known to be expressed by pancreatic β cells. We herein investigated the role of GLP-1R on T lymphocytes during immune response. Our data showed that a subset of T lymphocytes expresses GLP-1R, which is upregulated during alloimmune response, similarly to PD-1. When mice received islet or cardiac allotransplantation, an expansion of GLP-1R
pos T cells occurred in the spleen and was found to infiltrate the graft. Additional single-cell RNA sequencing (scRNA-seq) analysis conducted on GLP-1Rpos and GLP-1Rneg CD3+ T cells unveiled the existence of molecular and functional dissimilarities between both subpopulations, as the GLP-1Rpos are mainly composed of exhausted CD8 T cells. GLP-1R acts as a T cell-negative costimulatory molecule, and GLP-1R signaling prolongs allograft survival, mitigates alloimmune response, and reduces T lymphocyte graft infiltration. Notably, GLP-1R antagonism triggered anti-tumor immunity when tested in a preclinical mouse model of colorectal cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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