Faculty Opinions recommendation of NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells.

Author(s):  
Shiv Pillai
2016 ◽  
Vol 9 (2) ◽  
pp. 126-144 ◽  
Author(s):  
Yaping Sun ◽  
Matthew Iyer ◽  
Richard McEachin ◽  
Meng Zhao ◽  
Yi-Mi Wu ◽  
...  

STAT3 is a master transcriptional regulator that plays an important role in the induction of both immune activation and immune tolerance in dendritic cells (DCs). The transcriptional targets of STAT3 in promoting DC activation are becoming increasingly understood; however, the mechanisms underpinning its role in causing DC suppression remain largely unknown. To determine the functional gene targets of STAT3, we compared the genome-wide binding of STAT3 using ChIP sequencing coupled with gene expression microarrays to determine STAT3-dependent gene regulation in DCs after histone deacetylase (HDAC) inhibition. HDAC inhibition boosted the ability of STAT3 to bind to distinct DNA targets and regulate gene expression. Among the top 500 STAT3 binding sites, the frequency of canonical motifs was significantly higher than that of noncanonical motifs. Functional analysis revealed that after treatment with an HDAC inhibitor, the upregulated STAT3 target genes were those that were primarily the negative regulators of proinflammatory cytokines and those in the IL-10 signaling pathway. The downregulated STAT3-dependent targets were those involved in immune effector processes and antigen processing/presentation. The expression and functional relevance of these genes were validated. Specifically, functional studies confirmed that the upregulation of IL-10Ra by STAT3 contributed to the suppressive function of DCs following HDAC inhibition.


Author(s):  
Miriam A. Ossevoort ◽  
Monique J. Kleijmeer ◽  
Hans W. Nijman ◽  
Hans J. Geuze ◽  
W. Martin Kast ◽  
...  

AIDS ◽  
2007 ◽  
Vol 21 (13) ◽  
pp. 1683-1692 ◽  
Author(s):  
Nancy Connolly ◽  
Sharon Riddler ◽  
Joanna Stanson ◽  
William Gooding ◽  
Charles R Rinaldo ◽  
...  

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 277-285 ◽  
Author(s):  
M. Neumann ◽  
H.-W. Fries ◽  
C. Scheicher ◽  
P. Keikavoussi ◽  
A. Kolb-Mäurer ◽  
...  

Abstract A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-κB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-κB factors did not correlate with lower levels of cytosolic NF-κB inhibitors, the IκBs. One IκB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)


Nature ◽  
1995 ◽  
Vol 375 (6527) ◽  
pp. 151-155 ◽  
Author(s):  
Wanping Jiang ◽  
William J. Swiggard ◽  
Christine Heufler ◽  
Michael Peng ◽  
Asra Mirza ◽  
...  

1993 ◽  
Vol 178 (2) ◽  
pp. 479-488 ◽  
Author(s):  
K Inaba ◽  
M Inaba ◽  
M Naito ◽  
R M Steinman

Dendritic cells, while effective in sensitizing T cells to several different antigens, show little or no phagocytic activity. To the extent that endocytosis is required for antigen processing and presentation, it is not evident how dendritic cells would present particle-associated peptides. Evidence has now been obtained showing that progenitors to dendritic cells can internalize particles, including Bacillus Calmette-Guerin (BCG) mycobacteria. The particulates are applied for 20 h to bone marrow cultures that have been stimulated with granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce aggregates of growing dendritic cells. Cells within these aggregates are clearly phagocytic. If the developing cultures are exposed to particles, washed, and "chased" for 2 d, the number of major histocompatibility complex class II-rich dendritic cells increases substantially and at least 50% contain internalized mycobacteria or latex particles. The mycobacteria-laden, newly developed dendritic cells are much more potent in presenting antigens to primed T cells than corresponding cultures of mature dendritic cells that are exposed to a pulse of organisms. A similar situation exists when the BCG-charged dendritic cells are injected into the footpad or blood stream of naive mice. Those dendritic cells that have phagocytosed organisms induce the strongest T cell responses to mycobacterial antigens in draining lymph node and spleen. The administration of antigens to GM-CSF-induced, developing dendritic cells (by increasing both antigen uptake and cell numbers) will facilitate the use of these antigen-presenting cells for active immunization in situ.


1992 ◽  
Vol 175 (2) ◽  
pp. 609-612 ◽  
Author(s):  
S Nair ◽  
F Zhou ◽  
R Reddy ◽  
L Huang ◽  
B T Rouse

Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein can be achieved by delivering antigen in pH-sensitive liposomes to dendritic cells (DC) either in vivo or in vitro. Since the pH-sensitive liposome delivery system is efficient and easy to use, the approach promises to be valuable both in the study of basic mechanisms in antigen processing, and as a practical means of immunization.


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