GLP1R IS A T CELL NEGATIVE COSTIMULATORY MOLECULE

Glucagon Like Peptide-1 Receptor (GLP1R) is a key regulator of glucose metabolism, known to be expressed by pancreatic β-cells, gastric mucosa and hypothalamic appetite center. Recently, GLP1R mRNA has been detected on T lymphocytes; however, its function in these cells remains poorly understood. We herein investigated the extent of GLP1R expression in T lymphocytes and the role of its signalling during alloimmune response. Our data showed that, a subset of naïve CD4 and CD8 lymphocytes expresses GLP1R in humans and mice. When C57BL/6 mice received islet or cardiac allotransplantation from a fully mismatched BALB/c donors, an expansion of GLP1R+ CD4+/CD8+ cells occurred in the spleen and were found to infiltrate the graft at high percentage. Interestingly, the treatment with the GLP1R agonist Exenatide significantly prolonged cardiac and islet allograft survival and reduced graft T lymphocytes infiltrate. Interestingly, a strong synergism in mitigating alloimmunity was observed between Exenatide and Rapamycin. Mechanistically, mitogen stimulated CD4+GLP1R+ and CD8+ GLP1R+ T cells, showed significantly more cell death as compared to controls. Notably, our transcriptomic data on GLP1R+CD4+ and GLP1R+CD8+ T cells revealed/confirmed their tendency toward an apoptotic/anergic profile as compared to their counterparts untreated. In conclusion, GLP1R appeared to act as a negative costimulatory molecule and the GLP1R agonist Exenatide prolongs allograft survival, mitigates alloimmunity during alloimmune response, reduces T lymphocytes graft infiltration and skews the effector/regulatory T cell balance.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2023

Author dc:creator

• SEELAM, ANDY JOE

Contributors dc:contributor

• tutor: G. V. Zuccotti ; coordinatore: L. Pinotti
• A.J. Seelam
• ZUCCOTTI, GIAN VINCENZO
• PINOTTI, LUCIANO

• Settore MED/13 - Endocrinologia

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

http://dx.doi.org/10.13130/seelam-andy-joe_phd2023-03-30
10.13130/seelam-andy-joe_phd2023-03-30

OAI identifier oai:identifier

oai:air.unimi.it:2434/959499