ABSTRACT
T regulatory lymphocytes (Treg) expressing CCR5 exhibit strong suppression activity in various autoimmune disorders. However, there remains a lack of comprehensive understanding regarding their involvement in the development of type 1 diabetes (T1D). In this study, we examined the role of the CCR5/CCL5 axis in regulating inflammatory response and its impact on regulatory T cells in type 1 diabetes (T1D). We hypothesize that dysregulation of the CCR5/CCL5 axis contributes to the development and progression of T1D through modulation of Treg-dependent immune responses. We analyzed the expression levels of CCR5 on Tregs isolated from individuals with T1D, as well as the plasma concentration of its main ligands. We found that Tregs from T1D patients exhibited decreased expression of CCR5 compared to healthy controls. Additionally, we observed a correlation between the expression levels of CCR5 on Tregs and their immunosuppressive function in T1D patients. Our results indicate the impaired migratory capacity of CCR5 + Tregs, suggesting a possible link between the dysregulation of the CCR5/CCL5 axis and impaired immune regulation in T1D. In line with previous studies, our findings support the notion that dysregulation of the CCR5/CCL5 axis contributes to the development and progression of type 1 diabetes (T1D) by modulating Treg-dependent immune responses. The decreased expression of CCR5 on Tregs in T1D patients suggests a potential impairment in the migratory capacity of these cells, which could compromise their ability to suppress autoreactive T cells and maintain immune homeostasis. Furthermore, our study highlights the importance of CCR5 as a biomarker for identifying dysfunctional Tregs in T1D.
ABSTRACT
COVID-19 shows an unexplained, strong male bias for severity and mortality. Loss of Y (LOY) in myeloid cells is a risk factor candidate in COVID-19 because of associations with many age-related diseases and its effect on transcription of immune genes. We report the highest levels of LOY in cells that are crucial for the development of severe COVID-19 phenotype, such as low-density neutrophils, granulocytes, and monocytes reaching 46%, 32%, and 29%, respectively, from men with critical COVID-19 (n=139). LOY in sorted subpopulations of leukocytes correlated with increased thrombocyte count, thromboembolic events, invasive mechanical ventilation and a history of vessel disease. In recovered patients, LOY decreased in whole blood and peripheral blood mononuclear cells. Moreover, sc-RNA-seq analysis of CD14+ monocytes from 30 COVID-19 males and 34 controls revealed pervasive transcriptional downregulation in LOY-cells, notably affecting HLA class I and II genes important for antigen presentation. The data support a link between LOY and emergency myelopoiesis as well as the role of LOY in modulation of COVID-19 severity. Our results might also be relevant for other viral infections showing similar male bias.
