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 131
OP 137
DO 10.29074/ascls.2019002089
VO 32
IS 4
A1 Owaja, Claire
A1 Roback-Navarro, Evelyn
A1 Iwai, Naomi
A1 Lerret, Nadine
YR 2019
UL http://hwmaint.clsjournal.ascls.org/content/32/4/131.abstract
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.