Dendritic Cell Apoptosis: Regulation of Tolerance versus Immunity

Kushwah, Rahul

doi:10.4049/jimmunol.1000325

Cited by 95 publications

(92 citation statements)

References 83 publications

(89 reference statements)

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“…The mechanisms that govern whether IL-10 or TGF-b are produced after injection of ACs have not been elucidated, but may depend on either the provenance of the AC or its encounter with either macrophages or dendritic cells (25). Alternatively, the inflammatory milieu that occurs with Ag-induced arthritis may favor an IL-10 response after exposure to ACs.…”

Section: Discussionmentioning

confidence: 99%

Natural IgM Is Required for Suppression of Inflammatory Arthritis by Apoptotic Cells

Notley

Brown

Wright

et al. 2011

The Journal of Immunology

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The clearance of dying cells is vital for re-establishing tolerance during inflammation and has potent immunoregulatory consequences. Because natural IgM plays a key role in the removal of apoptotic cells, we investigated whether the immune modulatory properties of apoptotic cells depended on its presence. Using an Ab-independent, Ag-induced model of inflammatory arthritis, we tested whether natural IgM is essential for the arthritis-suppressing properties of apoptotic cells. Whereas administration of apoptotic cells reduced joint inflammation and damage in normal mice accompanied by suppression of the Th17 response, no protection was afforded in secreted IgM-deficient (Sμ–) mice. The enhanced production of IL-10 by T cells from draining lymph nodes and splenic marginal zone B cells, driven by the infusion of apoptotic cells, was abrogated in the absence of natural IgM. Apoptotic cells were present shortly after administration in the splenic marginal zone, but their removal was substantially delayed in the absence of natural IgM. Incubation of apoptotic cells with natural IgM in vitro restored their arthritis-suppressing properties in Sμ– mice. Moreover, these IgM-coated apoptotic cells were cleared rapidly after injection from the spleens of Sμ– mice. Our results demonstrate that natural IgM is a critical factor in a chain of events triggered by the administration of apoptotic cells that promote IL-10–secreting B and T cells and restrain the development of inflammation.

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Section: Discussionmentioning

confidence: 99%

Natural IgM Is Required for Suppression of Inflammatory Arthritis by Apoptotic Cells

Notley

Brown

Wright

et al. 2011

The Journal of Immunology

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“…45 In addition, it has been recently shown that uptake of apoptotic DCs induces immature DCs to secrete TGF-␤, which in turn promotes the differentiation of naive T cells into regulatory T cells. 46 Furthermore, constitutive ablation of DCs breaks selftolerance and results in spontaneous fetal autoimmunity. 47 Therefore, down-regulated miR-221 and up-regulated miRNA-155 expression during DC maturation by various stimuli, resulting in p27 kip1 accumulation in mDCs and subsequent DC apoptosis, could be physiologically important.…”

Section: Discussionmentioning

confidence: 99%

miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1

Huang

Zhang

et al. 2011

Blood

248

221

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“…Other functions of these DCs include regulating the influx of PMNs and rates of apoptosis. Exposure to LPS, as would occur in CF airways, induces the maturation and apoptosis of DCs, events that are critically involved in the development of tolerance versus immunogenicity (23,24). Airway epithelial cells are an important source of type I IFN effectors (25), and their expression is affected by CFTR mutations.…”

mentioning

confidence: 99%

Induction of Type I Interferon Signaling by Pseudomonas aeruginosa Is Diminished in Cystic Fibrosis Epithelial Cells

Parker

Cohen

Alhede

et al. 2012

Am J Respir Cell Mol Biol

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The clinical manifestations of infection in cystic fibrosis (CF) are restricted to the lung, and involve a limited number of pathogens, suggesting a specific defect in mucosal immunity. We postulated that cystic fibrosis transmembrane conductance regulator (CTFR) mutations could affect the activation of type I interferon signaling in airway epithelial cells, which function in immune surveillance and initiate the recruitment and activation of immune cells. In response to infection with Pseudomonas aeruginosa, Ifnb was induced more than 100-fold in the murine lung, and the phosphorylation of STAT1 was similarly induced by the expected TLR4/TRIF/MD2/TBK1 cascade. The stimulation by P. aeruginosa of CF (IB3) cells and control (C-38) human cell lines similarly resulted in the induction of IFN-b, but to a significantly lower extent in CF airway cells. The potential consequences of diminished type I IFN signaling were demonstrated in a murine model of P. aeruginosa pneumonia, pretreatment with polyinosinic:polycytidylic acid significantly enhanced bacterial clearance and correlated with increased numbers of mature CD11c 1 / CD86 1 dendritic cells (DCs) in the lung. Using culture supernatants from CF or control cell lines stimulated with P. aeruginosa, we similarly demonstrated the diminished activation of human monocytederived DCs by incubation with CF compared with normal epithelial cell culture supernatants, which was dependent on IFN-b. These observations suggest that dysfunction of the CFTR in airway epithelial cells may contribute to impaired immune surveillance in the CF airway and resultant colonization by P. aeruginosa.

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Dendritic Cell Apoptosis: Regulation of Tolerance versus Immunity

Cited by 95 publications

References 83 publications

Natural IgM Is Required for Suppression of Inflammatory Arthritis by Apoptotic Cells

Natural IgM Is Required for Suppression of Inflammatory Arthritis by Apoptotic Cells

miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1

Induction of Type I Interferon Signaling by Pseudomonas aeruginosa Is Diminished in Cystic Fibrosis Epithelial Cells

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