%0 Journal Article
%T Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule.
%A Ben Nasr M
%A Usuelli V
%A Dellepiane S
%A Seelam AJ
%A Fiorentino TV
%A D'Addio F
%A Fiorina E
%A Xu C
%A Xie Y
%A Balasubramanian HB
%A Castillo-Leon E
%A Loreggian L
%A Maestroni A
%A Assi E
%A Loretelli C
%A Abdelsalam A
%A El Essawy B
%A Uccella S
%A Pastore I
%A Lunati ME
%A Sabiu G
%A Petrazzuolo A
%A Ducci G
%A Sacco E
%A Centofanti L
%A Venturini M
%A Mazzucchelli S
%A Mattinzoli D
%A Ikehata M
%A Castellano G
%A Visner G
%A Kaifeng L
%A Lee KM
%A Wang Z
%A Corradi D
%A La Rosa S
%A Danese S
%A Yang J
%A Markmann JF
%A Zuccotti GV
%A Abdi R
%A Folli F
%A Fiorina P
%J Cell Metab
%V 36
%N 6
%D 2024 Jun 4
%M 38838642
%F 31.373
%R 10.1016/j.cmet.2024.05.001
%X 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-1Rpos 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.