TGF-β1 treated murine dendritic cells are maturation resistant and down-regulate Toll-like receptor 4 expression

Mou, Haibo; Miao, Lin; Cen, Hong; Yu, Jing; Meng, Xiaojian

doi:10.1631/jzus.2004.1239

Cited by 22 publications

(19 citation statements)

References 13 publications

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“…In this study, we showed that PMN-Ect inhibited the maturation of iMoDCs by LPS and induced new morphological and functional characteristics with a resulting reduced capacity to activate T cells. In addition, iMoDCs exposed to PMN-Ect released TGF-␤1 and it might well be that to some or a larger extent TGF-␤1 was responsible for the down-regulation of TLR4-mediated maturation of iDCs, as observed by others (15,34), and of surface expression of CCR7 (29). During DC maturation, the upregulated CCR7 is responsible for directing the migration of DCs to the lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Polymorphonuclear Neutrophil-Derived Ectosomes Interfere with the Maturation of Monocyte-Derived Dendritic Cells

Eken¹,

Gasser²,

Zenhaeusern

et al. 2008

The Journal of Immunology

168

165

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Polymorphonuclear neutrophils (PMNs) are a key component of the innate immune system. Their activation leads to the release of potent antimicrobial agents through degranulation. Simultaneously, PMNs release cell surface-derived microvesicles, so-called ectosomes (PMN-Ect). PMN-Ect are rightside-out vesicles with a diameter of 50–200 nm. They expose phosphatidylserine in the outer leaflet of their membrane and down-modulate monocyte/macrophage-activation in vitro. In this study, we analyzed the effects of PMN-Ect on maturation of human monocyte-derived dendritic cells (MoDCs). Intriguingly, exposing immature MoDCs to PMN-Ect modified their morphology, reduced their phagocytic activity, and increased the release of TGF-β1. When immature MoDCs were incubated with PMN-Ect and stimulated with the TLR4 ligand LPS, the maturation process was partially inhibited as evidenced by reduced expression of cell surface markers (CD40, CD80, CD83, CD86, and HLA-DP DQ DR), inhibition of cytokine-release (IL-8, IL-10, IL-12, and TNF-α), and a reduced capacity to induce T cell proliferation. Together these data provide evidence that PMN-Ect have the ability to modify MoDC maturation and function. PMN-Ect may thus represent an as yet unidentified host-factor influencing MoDC maturation at the site of injury, thereby possibly impacting on downstream MoDC-dependent immunity.

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Section: Discussionmentioning

confidence: 99%

Polymorphonuclear Neutrophil-Derived Ectosomes Interfere with the Maturation of Monocyte-Derived Dendritic Cells

Eken¹,

Gasser²,

Zenhaeusern

et al. 2008

The Journal of Immunology

168

165

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“…For example, transforming growth factor-beta (TGF-beta) is a cytokine expressed during lung development and is important for epithelial differentiation and maturation needed for surfactant synthesis [30]. Recent evidence indicates TGF-beta may also inversely regulate TLR4 expression [31,32]. The net effect may be promotion of epithelial surfactant synthesis while minimizing inflammation that could complicate respiratory function in the neonate.…”

Section: Discussionmentioning

confidence: 99%

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

Meyerholz

Kawashima

Gallup

et al. 2006

Developmental & Comparative Immunology

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Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep beta defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility. AbstractPreterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep beta defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p<0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208−) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208+/−) had significant (p<0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.

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“…Mou et al 44 observed that in vitro treatment of murine bone marrow-derived dendritic cells with TGF-β1 resulted in decreased expression of TLR4. This finding correlated with reduced sensitivity to lipopolysaccharide-induced maturation.…”

Section: Immunoregulation Of Dendritic Cells By Il-10mentioning

confidence: 99%

Immunoregulation of Dendritic Cells

Wallet¹,

Sen²,

Tisch

2005

Clinical Medicine & Research

122

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The paradigm of tolerogenic/immature versus inflammatory/mature dendritic cells has dominated the recent literature regarding the role of these antigen-presenting cells in mediating immune homeostasis or self-tolerance and response to pathogens, respectively. This issue is further complicated by the identification of distinct subtypes of dendritic cells that exhibit different antigen-presenting cell effector functions. The discovery of pathogen-associated molecular patterns and toll-like receptors provides the mechanistic basis for dendritic cell recognition of specific pathogens and induction of appropriate innate and adaptive immune responses. Only recently has insight been gained into how dendritic cells contribute to establishing and/or maintaining immunological tolerance to self. Soluble and cellular mediators have been reported to effectively regulate the function of dendritic cells by inducing several outcomes ranging from non-inflammatory dendritic cells that lack the ability to induce T lymphocyte activation to dendritic cells that actively suppress T lymphocyte responses. A thorough discussion of these stimuli and their outcomes is essential to understanding the potential for modulating dendritic cell function in the treatment of inflammatory disease conditions.

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TGF-β1 treated murine dendritic cells are maturation resistant and down-regulate Toll-like receptor 4 expression

Cited by 22 publications

References 13 publications

Polymorphonuclear Neutrophil-Derived Ectosomes Interfere with the Maturation of Monocyte-Derived Dendritic Cells

Polymorphonuclear Neutrophil-Derived Ectosomes Interfere with the Maturation of Monocyte-Derived Dendritic Cells

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

Immunoregulation of Dendritic Cells

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