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.
Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule / Ben Nasr, M., Usuelli, V., Dellepiane, S., Seelam, A.J., Fiorentino, T.V., D'Addio, F., Fiorina, E., Xu, C., Xie, Y., Balasubramanian, H.B., Castillo-Leon, E., Loreggian, L., Maestroni, A., Assi, E., Loretelli, C., Abdelsalam, A., El Essawy, B., Uccella, S., Pastore, I., Lunati, M.E., et al.. - In: CELL METABOLISM. - ISSN 1550-4131. - 36:6(2024), pp. 1302-1319. [10.1016/j.cmet.2024.05.001]
Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule
Corradi, Domenico;
2024-01-01
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-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
