PT  - JOURNAL ARTICLE
AU  - Claire Owaja
AU  - Evelyn Roback-Navarro
AU  - Naomi Iwai
AU  - Nadine Lerret
TI  - Hyperglycemia Activates the CD27-CD70 Axis on Human Peripheral Blood Mononuclear Cells
AID  - 10.29074/ascls.119.002089
DP  - 2020 Jan 01
TA  - American Society for Clinical Laboratory Science
PG  - ascls.119.002089
4099  - http://hwmaint.clsjournal.ascls.org/content/early/2020/01/06/ascls.119.002089.short
4100  - http://hwmaint.clsjournal.ascls.org/content/early/2020/01/06/ascls.119.002089.full
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.