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Immunomodulatory Mechanisms (immunomodulatory + mechanism)
Selected AbstractsCell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Monique E. Quaedackers Abstract Mesenchymal stromal cells regulate immune cell function via the secretion of soluble factors. Cell membrane interactions between these cell types may play an additional role. Here, we demonstrate that subpopulations of allo-activated T cells are capable of binding to human adipose-derived stromal cells (ASC). The bound T-cell population contained CD8+ T cells and was enriched for CD4,CD8, T cells, whereas the proportion of CD4+ T cells was decreased compared with the non-bound T-cell population. Bound CD4+ T cells had high proliferative activity and increased CD25 and FoxP3 expression. However, they also expressed CD127, excluding regulatory T-cell function. In CD8+ T cells, IL-2 sensitivity, as determined by the analysis of phosphorylated STAT5, was lower in the presence of ASC and even lower in bound cells. In contrast, IL-2-induced phosphorylated STAT5 levels were higher in bound CD4+ T cells than in non-bound CD4+ T cells. Additionally, pro-proliferative TGF-, signalling via endoglin and SMAD1/5/8 phosphorylation was detected in bound CD4+ T cells. Even after prolonged co-culture with ASC, the activated phenotype of bound CD4+ T cells persisted. In conclusion, these results demonstrate that the binding of lymphocytes to ASC represents an immunomodulatory mechanism in which CD8+ T cells are inhibited in their responsiveness to pro-inflammatory stimuli and reactive CD4+ T cells are depleted from the immune response. [source] High concentrations of the melatonin metabolite, N1 -acetyl- N,2 -formyl-5-methoxykynuramine, in cerebrospinal fluid of patients with meningitis: a possible immunomodulatory mechanismJOURNAL OF PINEAL RESEARCH, Issue 3 2005Sueli De Oliveira Silva Abstract:, We evaluated the presence of the melatonin metabolite N1 -acetyl- N2 -formyl-5-methoxykynuramine (AFMK), in cerebrospinal fluid (CSF) of patients with viral meningitis (n = 20) and control samples (n = 8) and correlate AFMK levels with inflammatory markers such as cellularity, protein, tumor necrosis factor (TNF)- ,, interleukin (IL)-8 and IL-1, levels. A portion of the CSF was extracted with dichloromethane (1:5) and analyzed by high-performance liquid chromatography (HPLC) under standardized conditions for AFMK. AFMK was detected in 16 of 20 CSF samples of patients with viral meningitis; the concentration of AFMK was found to be above the quantification limit (50 nmol/L) in six of these samples. AFMK was not detected in any of the eight control samples. The samples were classified into groups according to AFMK levels: undetectable (<10 nmol/L, group I), detectable but below the quantification limit (< 50 nmol/L, group II), and quantified (>50 nmol/L, group III). Group II presented the highest levels of proteins and IL-8, whereas group III showed the lowest levels of the inflammatory parameters. This study supports our hypothesis that inflammation favors the formation of AFMK and that this compound has immunomodulatory activity in vivo. [source] Antimicrobial peptides and proteins, exercise and innate mucosal immunityFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Nicholas P. West Abstract This review examines the question of whether exercise can be used as an experimental model to further our understanding of innate antimicrobial peptides and proteins (AMPs) and their role in susceptibility to infection at mucosal surfaces. There is strong evidence to suggest that AMPs, in combination with cellular and physical factors, play an important role in preventing infection. Although AMPs act directly on microorganisms, there is increasing recognition that they also exert their protective effect via immunomodulatory mechanisms, especially in noninflammatory conditions. Further studies that manipulate physiologically relevant concentrations of AMPs are required to shed light on the role they play in reducing susceptibility to infection. Evidence shows that in various form prolonged and/or exhaustive exercise is a potent modulator of the immune system, which can either sharpen or blunt the immune response to pathogens. The intensity and duration of exercise can be readily controlled in experimental settings to manipulate the degree of physical stress. This would allow for an investigation into a potential dose,response effect between exercise and AMPs. In addition, the use of controlled exercise could provide an experimental model by which to examine whether changes in the concentration of AMPs alters susceptibility to illness. [source] Regeneration, tissue injury and the immune responseJOURNAL OF ANATOMY, Issue 4 2006James W. Godwin Abstract The involvement of the immune system in the response to tissue injury has raised the possibility that it might influence tissue, organ or appendage regeneration following injury. One hypothesis that has been discussed is that inflammatory aspects may preclude the occurrence of regeneration, but there is also evidence for more positive roles of immune components. The vertebrate eye is an immunoprivileged site where inflammatory aspects are inhibited by several immunomodulatory mechanisms. In various newt species the ocular tissues such as the lens are regenerative and it has recently been shown that the response to local injury of the lens involves activation of antigen-presenting cells which traffic to the spleen and return to displace and engulf the lens, thereby inducing regeneration from the dorsal iris. The activation of thrombin from prothrombin in the dorsal iris is one aspect of the injury response that is important in the initiation of regeneration. The possible relationships between the immune response and the regenerative response are considered with respect to phylogenetic variation of regeneration in general, and lens regeneration in particular. [source] DNA Damage, Apoptosis and Langerhans Cells,Activators of UV-induced Immune Tolerance,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008Laura Timares Solar UVR is highly mutagenic but is only partially absorbed by the outer stratum corneum of the epidermis. UVR can penetrate into the deeper layers of the epidermis, depending on melanin content, where it induces DNA damage and apoptosis in epidermal cells, including those in the germinative basal layer. The cellular decision to initiate either cellular repair or undergo apoptosis has evolved to balance the acute need to maintain skin barrier function with the long-term risk of retaining precancerous cells. Langerhans cells (LCs) are positioned suprabasally, where they may sense UV damage directly, or indirectly through recognition of apoptotic vesicles and soluble mediators derived from surrounding keratinocytes. Apoptotic vesicles will contain UV-induced altered proteins that may be presented to the immune system as foreign. The observation that UVR induces immune tolerance to skin-associated antigens suggests that this photodamage response has evolved to preserve the skin barrier by protecting it from autoimmune attack. LC involvement in this process is not clear and controversial. We will highlight some basic concepts of photobiology and review recent advances pertaining to UV-induced DNA damage, apoptosis regulation, novel immunomodulatory mechanisms and the role of LCs in generating antigen-specific regulatory T cells. [source] Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, function as inhibitors of cellular and molecular components involved in type I interferon productionARTHRITIS & RHEUMATISM, Issue 7 2010Hideki Amuro Objective Statins, which are used as cholesterol-lowering agents, have pleiotropic immunomodulatory properties. Although beneficial effects of statins have been reported in autoimmune diseases, the mechanisms of these immunomodulatory effects are still poorly understood. Type I interferons (IFNs) and plasmacytoid dendritic cells (PDCs) represent key molecular and cellular pathogenic components in autoimmune diseases such as systemic lupus erythematosus (SLE). Therefore, PDCs may be a specific target of statins in therapeutic strategies against SLE. This study was undertaken to investigate the immunomodulatory mechanisms of statins that target the IFN response in PDCs. Methods We isolated human blood PDCs by flow cytometry and examined the effects of simvastatin and pitavastatin on PDC activation, IFN, production, and intracellular signaling. Results Statins inhibited IFN, production profoundly and tumor necrosis factor , production modestly in human PDCs in response to Toll-like receptor ligands. The inhibitory effect on IFN, production was reversed by geranylgeranyl pyrophosphate and was mimicked by either geranylgeranyl transferase inhibitor or Rho kinase inhibitor, suggesting that statins exert their inhibitory actions through geranylgeranylated Rho inactivation. Statins inhibited the expression of phosphorylated p38 MAPK and Akt, and the inhibitory effect on the IFN response was through the prevention of nuclear translocation of IFN regulatory factor 7. In addition, statins had an inhibitory effect on both IFN, production by PDCs from SLE patients and SLE serum,induced IFN, production. Conclusion Our findings suggest a specific role of statins in controlling type I IFN production and a therapeutic potential in IFN-related autoimmune diseases such as SLE. [source] | |||||||||||||