G protein-coupled receptor 37(GPR37) emerges as an important modulator of adenosinergic transmission in the striatum

G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein- coupled receptor, which suffers a defective parking ubiquitination in autosomal recessive Parkinson’s disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death (Takahashi and Imai, 2003). Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A2A receptor (A2AR) in the striatum (Morato et al., 2017;Sokolina et al., 2017).

Impaired T-cell differentiation in diabetic foot ulceration

Foot ulceration is one of the most debilitating complications associated with diabetes,but its cause remains poorly understood.Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing.However,few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes.In this study,we analysed the T-cell receptor(TCR)repertoire diversity in TCR-αβ^(+)T cells.We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers.Our results showed that diabetic individuals,especially those with foot ulcers,have a significantly lower naive T-cell number and a poorer TCR-Vβrepertoire diversity.We also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,which was even more pronounced in patients with acute foot ulceration.Moreover,the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients.In conclusion,effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers.This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.

Imbalance in T-cell differentiation as a biomarker of chronic diabetic foot ulceration

Diabetes is a growing epidemic due to the systematic increase in overweight and obesity,and chronic diabetic foot ulcers(DFUs)are the most debilitating and costly complication of diabetes.Prevention is still essential for DFU care,but early detection is limited because we do not have a good DFU biomarker.Here,we report the preliminary results of a large longitudinal study to test the effectiveness of the use of T-cell phenotype and TCR repertoire diversity as DFU biomarkers.Our results show that the ratio of effector/naïve T-cells and the number of TCR expansions are valuable biomarkers of DFU prognosis.