RESUMEN
Glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of glucose metabolism known to be expressed by pancreatic ß 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.
Asunto(s)
Receptor del Péptido 1 Similar al Glucagón , Trasplante de Islotes Pancreáticos , Ratones Endogámicos C57BL , Animales , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Ratones , Linfocitos T/inmunología , Linfocitos T/metabolismo , Masculino , Trasplante de Corazón , Ratones Endogámicos BALB C , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Supervivencia de Injerto/inmunologíaRESUMEN
An increasing body of research has demonstrated that appropriate stimulation of the meridians and acupoints in the human body can play a preventative and therapeutic role in diseases. This study combines the use of infrared thermography with intelligent electrophysiological diagnostic system (iEDS) to accurately diagnose and apply transdermal low-frequency electrical stimulation to treat abnormal meridians in patients with erectile dysfunction (ED). The treatment protocol included 6 treatments (each lasting 30 min and performed twice a week). The International Index of Erectile Function-5 (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Erection Hardness Scale were used to assess treatment results. A total of 62 patients were included in this study, with 31 patients in the treatment group and 31 patients in the sham therapy group. After six treatments, the treatment group improved significantly in IIEF-5 (15.52 ± 2.06 vs. 18.84 ± 2.67, p < 0.001), PHQ-9 (8.32 ± 6.33 vs. 4.87 ± 4.41, p < 0.001), GAD-7 (5.32 ± 5.08 vs. 2.94 ± 3.31, p = 0.003), and EHS (2.48 (2.00, 3.00) vs. 2.90 (2.00, 3.00), p = 0.007). After six sham treatment sessions, no improvements in any of the scores were reported in the sham therapy group. Following that, this group had an additional six treatments of regular therapy, which resulted in statistically significant improvements in IIEF-5 (16.65 ± 1.96 VS. 19.16 ± 2.40, p < 0.001), PHQ-9 (8.81 ± 6.25 VS. 4.97 ± 4.36, p < 0.001), GAD-7 (5.74 ± 5.18 VS. 3.68 ± 3.42, p < 0.001), and EHS (2.61 (2.00, 3.00) VS. 3.03 (2.00, 4.00), p = 0.003). No adverse events were reported regarding penile discomfort, pain, injury, or deformity. CLINICAL TRIALS: The study protocol is registered in the Clinical Trials Registry with the identification number ChiCTR2300070262.