Take home message: Vitamin D suppresses an immune response characterized by the increase of interleukin-12 secretion. Interleukin-12 has been implicated in the immune response cascade leading to an increased inflammatory intestinal response that may be a factor in certainly a symptom of Crohn's Disease, if not a suspected cause of Crohn's Disease.
TGF-B and Vitamin D3 Utilize Distinct Pathways to Suppress IL-12 Production and Modulate Rapid Differentiation of Human Monocytes into CD83 Dendritic Cells
Lyudmila A. Lyakh, Michael Sanford, Sebel Chekol, Howard A. Young, and Anita B. Roberts
ABSTRACT - We previously demonstrated that agents known to signal infection or inflammation can rapidly and directly drive differentiation of human CD14 monocytes into CD83 dendritic cells (DCs) when introduced to cells under serum-free conditions. In this study, we evaluated the effects of TGF-B and vitamin D3 (VitD3) on the proportion and function of monocytes that adopt DC characteristics. TGF-B significantly decreased the proportion of cells that rapidly adopted stable DC characteristics in response to LPS, but had little or no effect on calcium ionophore-induced differentiation. In contrast, VitD3 showed no such pathway specificity and dramatically suppressed differentiation of monocytes into DCs in response to these agents. Both TGF-B and VitD3 altered cytokine and chemokine production in LPS-treated monocytes, inhibited IL-12 and IL-10 secretion, and decreased the functional capacity of DCs. Despite the similar effects of TGF- and VitD3, there are significant differences in the signaling pathways used by these agents, as evidenced by their distinct effects on LPS- and calcium ionophore-induced DC differentiation, on LPS-induced secretion of IL-10, and on two members of the NF-B family of transcription factors, RelB and cRel. These studies identify TGF-B and VitD3 as potent regulatory factors that use distinct pathways to suppress both the differentiation of DCs as well as their capacity to secrete the Th1-polarizing cytokine IL-12. Because these agents are present in serum and negatively affect DC differentiation at physiological concentrations, our findings are likely to have significance regarding the in vivo role of TGF-B and VitD3 in determining the type of immune responses.
The Journal of Immunology, 2005, 174: 2061–2070.
Read the entire article www.jimmunol.org/content/174/4/2061.full.pdf
