Circulating dendritic cell number and intracellular TNF-[alpha] production in women with type 2 diabetes

Human dendritic cell (DC) subsets perform specialized functions for surveillance against bacterial and viral infections essential for the management of type 2 diabetes (T2D). Production of tumor necrosis factor-alpha (TNF-[alpha]) by DCs acts in autocrine fashion to regulate DC maturation and promotes the inflammatory response. This study was designed to compare circulating DC number and intracellular TNF-[alpha] production between post-menopausal women with T2D and healthy women. Blood samples were obtained (n = 21/group) and examined for plasma glucose and TNF-[alpha] concentrations, and dendritic cell subset immunophenotype (plasmacytoid, pDC, CD85k(ILT-3)^sup +^CD123^sup +^CD16^sup -^CD14^sup -^ and myeloid, mDC, CD85k(ILT-3)^sup +^CD33^sup +^CD123^sup dim to neg^CD16^sup -^CD14^sup dim to neg^). Intracellular production of TNF-[alpha] was determined in unstimulated and stimulated DCs. Women with T2D had significantly (P < 0.05) greater plasma glucose and TNF-[alpha] concentrations when compared to healthy women. Women with T2D having poor glycemic control (T2D Poor Control, HbA1c ≥ 7%) had fewer circulating pDCs than women with T2D having good glycemic control (T2D Good Control, HbA1c < 7%) and healthy women. A significant interaction (P = 0.011) was observed between the effects of plasma glucose and group for intracellular expression of TNF-[alpha] in stimulated pDCs. Intracellular production of TNF-[alpha] in pDCs was significantly greater in healthy vs. T2D Poor Control (P < 0.0001) and T2D Good Control (P < 0.0001) but did not differ between T2D subgroups. The mDC number and intracellular production of TNF-[alpha] did not differ between groups. These findings indicate that TNF-[alpha] production by pDCs was reduced in women with T2D and circulating number of pDCs was associated with glycemic control.[PUBLICATION ABSTRACT]