Calcium signaling inhibits interleukin-12 production and activates CD83 + dendritic cells that induce Th2 cell development

Mark B. Faries, Isabelle Bedrosian, Shuwen Xu, Gary Koski, James G. Roros, Mirielle A. Moise, Hung Q. Nguyen, Friederike H.C. Engels, Peter A. Cohen, Brian J. Czerniecki

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57 Scopus citations

Abstract

Mature dendritic cells (DCs), in addition to providing costimulation, can define the Th1, in contrast to the Th2, nature of a T-cell response through the production of cytokines and chemokines. Because calcium signaling alone causes rapid DC maturation of both normal and transformed myeloid cells, it was evaluated whether calcium-mobilized DCs polarize T cells toward a Th1 or a Th2 phenotype. After human monocytes were cultured for 24 hours in serum-free medium and granulocyte-macrophage colony-stimulating factor to produce immature DCs, additional overnight culture with either calcium ionophore (CI) or interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble CD40L resulted in phenotypically mature DCs that produced interleukin-8 (IL-8) and displayed marked expression of CD80, CD86, CD40, CD54, CD83, DCLAMP, and RelB. DCs matured by IFN-γ, TNF-α, and soluble CD40L were additionally distinguished by undetectable CD4 expression, marked secretion of IL-12, IL-6, and MIP-1β, and preferential ability to promote Th1/Tc1 characteristics during T-cell sensitization. In contrast, DCs matured by CI treatment were distinguished by CD4 expression, modest or absent levels of IL-12, IL-6, and MIP-1β, and preferential ability to promote Th2/ Tc2 characteristics. Calcium signaling selectively antagonized IL-12 production by mature DCs activated with IFN-γ, and soluble CD40L. Although the activation of DCs by calcium signals is largely mediated through calcineurin phosphatase, the inhibition of IL-12 production by calcium signaling was independent of this enzyme. Naturally occurring calcium fluxes in immature DCs, therefore, negatively regulate Dc1 differentiation while promoting Dc2 characteristics and Th2/Tc2 polarization. Calcium-mobilized DCs may have clinical usefulness in treating disease states with excessive Th1/Tc1 activity, such as graft-versus-host disease or autoimmunity.

Original languageEnglish (US)
Pages (from-to)2489-2497
Number of pages9
JournalBlood
Volume98
Issue number8
DOIs
StatePublished - Oct 15 2001

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Faries, M. B., Bedrosian, I., Xu, S., Koski, G., Roros, J. G., Moise, M. A., Nguyen, H. Q., Engels, F. H. C., Cohen, P. A., & Czerniecki, B. J. (2001). Calcium signaling inhibits interleukin-12 production and activates CD83 + dendritic cells that induce Th2 cell development. Blood, 98(8), 2489-2497. https://doi.org/10.1182/blood.V98.8.2489