TGF-β and Vitamin D3 Utilize Distinct Pathways to Suppress IL-12 Production and Modulate Rapid Differentiation of Human Monocytes into CD83+ Dendritic Cells
- 15 February 2005
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 174 (4), 2061-2070
- https://doi.org/10.4049/jimmunol.174.4.2061
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-β and vitamin D3 (VitD3) on the proportion and function of monocytes that adopt DC characteristics. TGF-β 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-β 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-β 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-κB family of transcription factors, RelB and cRel. These studies identify TGF-β 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-β and VitD3 in determining the type of immune responses.Keywords
This publication has 74 references indexed in Scilit:
- Using Signaling Pathways to Overcome Immune Tolerance to TumorsScience's STKE, 2004
- Toll-like receptor signallingNature Reviews Immunology, 2004
- Dendritic cells: emerging pharmacological targets of immunosuppressive drugsNature Reviews Immunology, 2004
- Regulation of 25-hydroxyvitamin D3-1α-hydroxylase and production of 1α,25-dihydroxyvitamin D3 by human dendritic cellsBlood, 2003
- RETRACTED: The immune decision toward allograft tolerance in non-human primates requires early inhibition of innate immunity and induction of immune regulationTransplant Immunology, 2003
- 1α,25-Dihydroxyvitamin D3 Increases TGF β1 Binding to Human OsteoblastsBiochemical and Biophysical Research Communications, 2002
- Transforming growth factor-β in T-cell biologyNature Reviews Immunology, 2002
- Role of transforming growth factor beta in cancerJournal of Cellular Physiology, 2001
- I kappa B epsilon, a novel member of the Ikappa B family, controls RelA and cRel NF-kappa B activityThe EMBO Journal, 1997
- Mechanism of activation of the TGF-β receptorNature, 1994