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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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
Externally publishedYes

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Th2 Cells
Calcium Signaling
Interleukin-12
Dendritic Cells
Calcium
CD40 Ligand
T-cells
Interferons
Calcium Ionophores
T-Lymphocytes
Interleukin-6
Tumor Necrosis Factor-alpha
Serum-Free Culture Media
Graft vs Host Disease
Myeloid Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Autoimmunity
Interleukin-8
Chemokines
Grafts

ASJC Scopus subject areas

  • Hematology

Cite this

Faries, M. B., Bedrosian, I., Xu, S., Koski, G., Roros, J. G., Moise, M. 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

Calcium signaling inhibits interleukin-12 production and activates CD83 + dendritic cells that induce Th2 cell development. / Faries, Mark B.; Bedrosian, Isabelle; Xu, Shuwen; Koski, Gary; Roros, James G.; Moise, Mirielle A.; Nguyen, Hung Q.; Engels, Friederike H C; Cohen, Peter A; Czerniecki, Brian J.

In: Blood, Vol. 98, No. 8, 15.10.2001, p. 2489-2497.

Research output: Contribution to journalArticle

Faries, MB, Bedrosian, I, Xu, S, Koski, G, Roros, JG, Moise, MA, Nguyen, HQ, Engels, FHC, Cohen, PA & Czerniecki, BJ 2001, 'Calcium signaling inhibits interleukin-12 production and activates CD83 + dendritic cells that induce Th2 cell development', Blood, vol. 98, no. 8, pp. 2489-2497. https://doi.org/10.1182/blood.V98.8.2489
Faries, Mark B. ; Bedrosian, Isabelle ; Xu, Shuwen ; Koski, Gary ; Roros, James G. ; Moise, Mirielle A. ; Nguyen, Hung Q. ; Engels, Friederike H C ; Cohen, Peter A ; Czerniecki, Brian J. / Calcium signaling inhibits interleukin-12 production and activates CD83 + dendritic cells that induce Th2 cell development. In: Blood. 2001 ; Vol. 98, No. 8. pp. 2489-2497.
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AU - Roros, James G.

AU - Moise, Mirielle A.

AU - Nguyen, Hung Q.

AU - Engels, Friederike H C

AU - Cohen, Peter A

AU - Czerniecki, Brian J.

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