Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection
Tatiana KisselevaMaren von Köckritz‐BlickwedeDonna ReichartShauna M. McGillvrayGerhard WingenderMitchell KronenbergChristopher K. GlassVictor NizetDavid A. Brenner
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Fibrocyte
Cathelicidin
This chapter contains sections titled: Introduction Dendritic cell terminology and heterogeneity Antigen uptake Antigen presentation Integrated function of dendritic cells in the immune response Role for dendritic cells in allergic sensitization in humans Dendritic cells in allergic asthma Dendritic cells in atopic dermatitis Role of dendritic cells in allergic rhinitis Dendritic cells as drug targets in allergic diseases Origin and function of macrophages Homeostasis in the alveolar compartment is maintained by alveolar macrophages Function of alveolar macrophages in inflammatory conditions and asthma Conclusion References
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Abstract Background Vitamin D plays a protective role in ulcerative colitis (UC) patients through unclear mechanisms. Cathelicidin is an antimicrobial peptide induced by 1,25(OH)D2. Our goal was to evaluate the link between cathelicidin and vitamin D–associated clinical outcomes in UC patients, explore vitamin D induction of cathelicidin in human colon cells, and evaluate the effects of intrarectal human cathelicidin on a murine model of colitis. Methods Serum and colonic cathelicidin levels were measured in UC patients and correlated with clinical and histologic outcomes. Human colon cells were treated with 1,25(OH)2D and production of cathelicidin and cytokines were quantified. Antimicrobial activity against Escherichia coli from cell culture supernatants was measured. Mice were treated with intrarectal cathelicidin, and its effects on DSS colitis and intestinal microbiota were evaluated. Results In UC patients, serum 25(OH)D positively correlated with serum and colonic cathelicidin. Higher serum cathelicidin is associated with decreased risk of histologic inflammation and clinical relapse but not independent of 25(OH)D or baseline inflammation. The 1,25(OH)2D treatment of colon cells induced cathelicidin and IL-10, repressed TNF-α, and suppressed Escherichia coli growth. This antimicrobial effect was attenuated with siRNA-cathelicidin transfection. Intrarectal cathelicidin reduced the severity of DSS colitis but did not mitigate the impact of colitis on microbial composition. Conclusions Cathelicidin plays a protective role in 25(OH)D-associated UC histologic outcomes and murine colitis. Cathelicidin is induced by vitamin D in human colonic epithelial cells and promotes antimicrobial activity against E. coli. Our study provides insights into the vitamin D–cathelicidin pathway as a potential therapeutic target.
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The human cathelicidin-18 is an antimicrobial, immunomodulatory and tissue repair peptide. The LL-37 fragment of this peptide which is in fact the active domain of the cathelicidin-18 is critical for the human antibacterial defense and epithelial integrity. It's activity against resistant pathogens, the potential of epithelial healing after microbial injury and the neutralization of bacterial endotoxin underlie the most important benefits of this peptide. However, there are still a number of questions that remain to be answered regarding the precise interactions of cathelicidin-18 within the immune system, the exact tissue concentrations or its possible pro-tumoral activity. In this respect, the therapeutic potential of cathelicidin-18 in various infections has been proved by in vitro experiments, but additional detailed clinical studies are still required to ascertain its antimicrobial role in vivo. We present a short review on the antibacterial activity of human cathelicidin-18 (LL-37) according to in vitro experiments while discussing its potential use in the clinical practice.
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Objective To observe the interference of Feiliuping Extractum and its modified formulas on the antigen presentation of dendritic cells in cultural system in vitro and study the molecular mechanism.Methods The inducing cultural system was established to induce and differentiate mature dendritic cells in human peripheral blood mononuclear cells(PBMC),ie.PBMC were separated from peripheral blood of healthy people.The cytokines(TNFα,IL-4 and GM-CSF) were used jointly to induce and obtain the mature dendritic cells in differentiation and function.The interference of Feiliuping Extractum and its modified formulas to dendritic cells and the expressions of related surface molecules to antigen presentation were detected by using flow cytometry,and their influence on the content of IL-12 secreted by dendritic cells were studied.Results Feiliuping Extractum up-regulated the expressions of dendritic cells and related cytomembrane molecules to antigen presentation,such as MHC-Ⅱ,CD80,CD83,CD86 and CD40 and promoted the IL-12 content secreted by dendritic cells.Conclusion Feiliuping Extractum can regulate antigen presentation of dendritic cells and improve the body function of anti-tumor immunological surveillance.
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Abstract Dendritic cell (DC) and macrophage are the powerful antigen presenting cells. These show remarkable antigen processing function. It has been reported that antigen processing is enhanced by adjuvant. In DC and macrophage, LPS or IFNγ induces cell proliferation, cytokine production, antigen presentation to naive T cell. Among DC subset, CD8 positive DC enhances autophagy function especially in cross presentation. It is still nuclear how DC processes antigen by ubiquitin proteasome pathway or by autophagy pathway. To induce more effective immune response on vaccination or immune therapy, we study the effect of adjuvant treatment for autophagy function in DC and macrophage. Three types of different culture condition were used to establish DC subsets and compared to those function of macrophage. Then analyzed the antigen processing capacity as well as the autophagy function. We induced DC in vitro culture with GM-CSF, GM-CSF with IL-4, GM-CSF with IL-15, then stimulated DCs or macrophage by using LPS or IFNγ for up to 24 hours before antigen uptake. On antigen uptake and processing, GM-CSF induced or GM-CSF with IL-15 induced DC showed antigen processing, however GM-CSF with IL-4 induced DC showed active antigen processing within 60 min. Contrary to active antigen processing, GM-CSF with IL-14 –DC did not show any inducible effect after adjuvant treatment, but GM-CSF or GM-CSF with IL-15-DC increased the autophagy function. On the other hand, macrophage could not obtain autophagy effect thorough adjuvant treatment. DCs were studied the gene expression of cytokines, cell surface molecules such as co-stimulation molecules, mannose receptor, to evaluate antigen uptake capacity, processing pattern and autophagy.
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Abstract The model that dendritic cell (DC) “maturation” describes the change from an immature, antigen-capturing cell to a mature, antigen-presenting cell is well-established. Classification of DCs in terms of function has been problematic previously. It is therefore proposed that mature and not immature DCs are responsible for antigen presentation and stimulation of T cells. Furthermore, DC antigen presentation to T cells can have two outcomes: tolerance or immunity. The particular outcomes appear to be determined by the activation state of the mature DC. DCs can be activated by a range of environmental stimuli or “danger signals”. Here, the hypothesis is advanced that activated, mature DCs induce T cell immunity, and resting, nonactivated but fully differentiated mature antigen-presenting DCs can induce tolerance. This proposal extends to conventional DCs and plasmacytoid DCs. The paper also concentrates on the spleen as a site for DC maturation, in light of evidence from this laboratory for differentiation of DCs from splenic precursors in long-term, stroma-dependent cultures. The hypothesis advanced here serves to simplify many current issues regarding DC maturation and function.
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Dendritic cells are specialized cells of the innate immune system, with high capacity to present antigens in the context of the Major Histocompatibility Complex II (MHC-II) to T lymphocytes (CD4+); these cells are up to 100 times stronger than any other antigen presenting cell. The ability of the antigen presentation by dendritic cells has been documented in animal models and clinical studies conducted in humans. Based on the above, different techniques and methods have been developed to use dendritic cells in cancer-aimed immunotherapies. The dendritic cell vaccines refer to biological therapies, prepared by different strategies (ex vivo and in vivo), which aim to enhance the presentation of tumor antigens and develop a more targeted and sustained immune response on these. They are obtained from precursor cells that mature with specific stimuli that direct them to the desired therapy. Different applications for these therapies have been described in numerous types of cancers, which will be described.
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