RT Journal Article
SR Electronic
T1 Hyperglycemia Activates the CD27-CD70 Axis on Human Peripheral Blood Mononuclear Cells
JF American Society for Clinical Laboratory Science
JO Clin Lab Sci
FD American Society of Chemistry and Laboratory Science
SP ascls.119.002089
DO 10.29074/ascls.119.002089
A1 Claire Owaja
A1 Evelyn Roback-Navarro
A1 Naomi Iwai
A1 Nadine Lerret
YR 2020
UL http://hwmaint.clsjournal.ascls.org/content/early/2020/01/06/ascls.119.002089.abstract
AB Obesity is now strongly associated with chronic low-grade inflammation that, without intervention, contributes to the development of pre-diabetes and eventually Type 2 diabetes. While the exact mechanism that inflammation plays in the pathogenesis from obesity to Type 2 diabetes is unclear, activated immune cells and pro-inflammatory cytokines have been found in the adipose tissue of Type 2 diabetics, implicating their role in the disease process. The CD27-CD70 pathway provides a crucial inflammatory co-stimulatory signal, with CD70 being expressed on activated antigen presenting cells, and CD27 expressed on lymphocytes. While the CD27-CD70 axis is being explored in other models of chronic inflammation, such as rheumatoid arthritis and colitis, the role played in Type 2 diabetes remains unknown. Here we report the downregulation of CD27 on CD4 T cells when co-cultured with dendritic cells primed in increasing concentrations of glucose, indicating an effector phenotype of these T cells. Importantly, we also highlight that CD70 is concurrently upregulated on dendritic cells primed in high concentrations of glucose, resulting in increased production of IFN-γ and TNF-α by the CD70 expressing dendritic cells, when compared to dendritic cells primed in a lower concentration of glucose. These results reveal a novel role for CD27-CD70 interactions in the pathogenesis of Type 2 diabetes and provide support for future investigations into this pathway. Additionally, CD27 could be analyzed as a way to further stratify pre-diabetic patients and guide diagnosticians towards the most efficient therapy.