PT  - JOURNAL ARTICLE
AU  - Owaja, Claire
AU  - Roback-Navarro, Evelyn
AU  - Iwai, Naomi
AU  - Lerret, Nadine
TI  - Hyperglycemia Activates the CD27-CD70 Axis on Human Peripheral Blood Mononuclear Cells
AID  - 10.29074/ascls.2019002089
DP  - 2019 Oct 01
TA  - American Society for Clinical Laboratory Science
PG  - 131--137
VI  - 32
IP  - 4
4099  - http://hwmaint.clsjournal.ascls.org/content/32/4/131.short
4100  - http://hwmaint.clsjournal.ascls.org/content/32/4/131.full
SO  - Clin Lab Sci2019 Oct 01; 32
AB  - Obesity is now strongly associated with chronic low-grade inflammation that, without intervention, contributes to the development of prediabetes and eventually type 2 diabetes. Although the exact mechanism that inflammation plays in the pathogenesis from obesity to type 2 diabetes is unclear, activated immune cells and proinflammatory cytokines have been found in the adipose tissue of people with type 2 diabetes, implicating their role in the disease process. The CD27-CD70 pathway provides a crucial inflammatory costimulatory signal, with CD70 being expressed on activated antigen-presenting cells and CD27 expressed on lymphocytes. Although 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. This article reports the downregulation of CD27 on CD4 T cells when cocultured with dendritic cells primed in increasing concentrations of glucose, indicating an effector phenotype of these T cells. Importantly, it is also highlighted that CD70 is concurrently upregulated on dendritic cells primed in high concentrations of glucose, which results in increased production of interferon-γ and tumor necrosis factor α by the CD70 expressing dendritic cells when compared with 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 to further stratify patients with prediabetes and guide diagnosticians towards the most efficient therapy.