Exposure of myeloid dendritic cells to exogenous or endogenous IL-10 during maturation determines their longevity

W. L William Chang, Nicole Baumgarth, Meghan K. Eberhardt, C. Y Daniel Lee, Colin A. Baron, Jeffrey Gregg, Peter A Barry

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Abstract

Dendritic cells (DC) are essential for the initiation of primary adaptive immune responses, and their functionality is strongly down-modulated by IL-10. Both innate and adaptive immune signals trigger the up-regulation of antiapoptotic Bcl-2 family members to facilitate the survival of DCs after maturation. However, whether IL-10 alters the expression of apoptotic-related genes in maturing DCs has not been determined. In this study, we demonstrate that spontaneous apoptosis rapidly occurred in myeloid DCs exposed to exogenous IL-10 upon maturation. Microarray analysis indicates that IL-10 suppressed the induction of three antiapoptotic genes, bcl-2, bcl-x, and bfl-1, which was coincident with the increased sensitivity of mature DCs to spontaneous apoptosis. IL-10 markedly inhibited the accumulation of steady state Bcl-2 message and protein in myeloid DCs activated through TLRs or TNFR family members, whereas exogenous IL-10 affected Bcl-xL expression in a moderate manner. In contrast, bcl-2 expression of plasmacytoid DCs was less sensitive to the effects of IL-10. We further show that autocrine IL-10 significantly limited the longevity of myeloid DCs and altered the expression kinetics of Bcl-2 but not Bcl-xL in maturing DCs. We conclude that the degree of IL-10 exposure and/or the level of endogenous IL-10 production upon myeloid DC maturation play a critical role in determining DC longevity. This regulatory mechanism of IL-10 is associated with the dynamic control of antiapoptotic Bcl-2 proteins.

Original languageEnglish (US)
Pages (from-to)7794-7804
Number of pages11
JournalJournal of Immunology
Volume178
Issue number12
StatePublished - Jun 15 2007

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Myeloid Cells
Interleukin-10
Dendritic Cells
Apoptosis
bcl-2 Genes
Adaptive Immunity
Microarray Analysis
Proteins
Up-Regulation

ASJC Scopus subject areas

  • Immunology

Cite this

Exposure of myeloid dendritic cells to exogenous or endogenous IL-10 during maturation determines their longevity. / Chang, W. L William; Baumgarth, Nicole; Eberhardt, Meghan K.; Lee, C. Y Daniel; Baron, Colin A.; Gregg, Jeffrey; Barry, Peter A.

In: Journal of Immunology, Vol. 178, No. 12, 15.06.2007, p. 7794-7804.

Research output: Contribution to journalArticle

Chang, W. L William ; Baumgarth, Nicole ; Eberhardt, Meghan K. ; Lee, C. Y Daniel ; Baron, Colin A. ; Gregg, Jeffrey ; Barry, Peter A. / Exposure of myeloid dendritic cells to exogenous or endogenous IL-10 during maturation determines their longevity. In: Journal of Immunology. 2007 ; Vol. 178, No. 12. pp. 7794-7804.
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abstract = "Dendritic cells (DC) are essential for the initiation of primary adaptive immune responses, and their functionality is strongly down-modulated by IL-10. Both innate and adaptive immune signals trigger the up-regulation of antiapoptotic Bcl-2 family members to facilitate the survival of DCs after maturation. However, whether IL-10 alters the expression of apoptotic-related genes in maturing DCs has not been determined. In this study, we demonstrate that spontaneous apoptosis rapidly occurred in myeloid DCs exposed to exogenous IL-10 upon maturation. Microarray analysis indicates that IL-10 suppressed the induction of three antiapoptotic genes, bcl-2, bcl-x, and bfl-1, which was coincident with the increased sensitivity of mature DCs to spontaneous apoptosis. IL-10 markedly inhibited the accumulation of steady state Bcl-2 message and protein in myeloid DCs activated through TLRs or TNFR family members, whereas exogenous IL-10 affected Bcl-xL expression in a moderate manner. In contrast, bcl-2 expression of plasmacytoid DCs was less sensitive to the effects of IL-10. We further show that autocrine IL-10 significantly limited the longevity of myeloid DCs and altered the expression kinetics of Bcl-2 but not Bcl-xL in maturing DCs. We conclude that the degree of IL-10 exposure and/or the level of endogenous IL-10 production upon myeloid DC maturation play a critical role in determining DC longevity. This regulatory mechanism of IL-10 is associated with the dynamic control of antiapoptotic Bcl-2 proteins.",
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AU - Gregg, Jeffrey

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