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Immune Disorders (immune + disorders)
Selected AbstractsGenetic variations associated with psoriasis and psoriatic arthritis found by genome-wide associationDERMATOLOGIC THERAPY, Issue 2 2010Kristina Callis Duffin ABSTRACT Psoriasis and psoriatic arthritis are immune disorders with a complex polygenic basis. HLA-Cw6, which lies in the major histocompatibility region on chromosome 6, is considered the major genetic determinant of psoriasis. Recent genome-wide association studies have identified new variants outside of the MHC with relevance to the immunology of psoriasis. Variants in or near genes that encode subunits of cytokines (IL12B, IL23A) or cytokine receptors (IL23R) are interesting given that the gene product of IL12B, p40, is the target of a recently approved monoclonal antibody therapy for psoriasis (ustekinumab). Association with psoriasis and psoriatic arthritis has been found in TNFAIP3 and TNFIP1, ubiquitin ligases in the NF-,B pathway, and IL13, a Th2 cytokine. Copy number variation of human beta-defensin and late cornified envelope genes also associate with psoriasis. Many of these genetic variations also associate with immune disorders considered psoriatic co-morbidities, including Crohn's disease and diabetes. [source] Bifidobacterium longum lysate, a new ingredient for reactive skinEXPERIMENTAL DERMATOLOGY, Issue 8 2010Audrey Guéniche Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2010; 19: e1,e8. Abstract:, Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3,1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin. [source] Natural killer cell cytotoxicity: how do they pull the trigger?IMMUNOLOGY, Issue 1 2009Nicola J. Topham Summary Natural killer (NK) cells target and kill aberrant cells, such as virally infected and tumorigenic cells. Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell. The essential role that secretory lysosome exocytosis plays in the cytotoxic function of NK cells is highlighted by immune disorders that are caused by the mutation of critical components of the exocytic machinery. This review will discuss recent studies on the molecular basis for NK cell secretory lysosome exocytosis and the immunological consequences of defects in the exocytic machinery. [source] Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002Abhijit Chakraborty Abstract Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine under investigation for strong antiinflammatory properties, are being contemplated as a potential joint therapeutic regimen in immune disorders. Their pharmacodynamic interactions were examined in blood from healthy adult male and female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole,blood lymphocyte proliferation technique. Isobolograms along with parametric competitive and noncompetitive interaction models were used to determine the nature and intensity of interactions. Single drug effects show prednisolone more efficacious in inhibiting lymphocyte proliferation with an IC50 of 3.3 ng/mL and Imax value of 1, signifying complete suppression. Analogous parameters for IL-10 were 16.2 ng/mL for IC50 and 0.89 for Imax. There were no significant differences in the single drug immunosuppressive effects among genders. Their joint effects showed additive interaction based on isobolographic analysis. Parametric analysis using the competitive interaction model described their interaction as slightly synergistic, while the noncompetitive interaction modeling indicate a small degree of antagonism. Also, the joint effects in females tend to be more antagonistic than males. Concomitant use of prednisolone and IL-10 should thus reflect the net additive responses to concentrations of each agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1334,1342, 2002 [source] The immunocompromised district: a unifying concept for lymphoedematous, herpes-infected and otherwise damaged sitesJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 12 2009V Ruocco Abstract Systemic immunodeficiency is known to facilitate the onset of opportunistic infections, tumours and immune disorders in any district of the body. There are clinical events, such as chronic lymphoedema, herpetic infections, vaccinations and heterogeneous physical injuries which can selectively damage and immunologically mark the cutaneous district they act upon. After the causing event has disappeared, the affected district may appear clinically normal, but its immune behaviour is often compromised forever. An immunocompromised district becomes a site which is particularly susceptible to subsequent outbreaks of opportunistic infections, tumours and immune disorders confined to the district itself. In this review, there is an ample case-report collection of opportunistic disorders (infectious, neoplastic, immune) which appeared in immunocompromised districts. The cases have been grouped according to the clinical settings responsible for the local immune imbalance: regional chronic lymphoedema; herpes-infected sites, which feature the well-known Wolf's isotopic response; and otherwise damaged areas, comprising sites of vaccination, ionizing or UV radiation, thermal burns and traumas. Whatever the immunocompromising factor, a common denominator which facilitates the occurrence of tumours, infections and dysimmune reactions in an immunocompromised district may reside in locally hampered lymph drainage and/or locally altered neuromediator signalling. In fact, any obstacle to the normal trafficking of immunocompetent cells through lymphatic channels or any interference with the signals that the neuropeptides and neurotransmitters released by peripheral nerves send to cell membrane receptors of immunocompetent cells, can significantly alter the local immune response, thus paving the way for heterogeneous opportunistic disorders in the immunocompromised district. [source] The importance of early complementary feeding in the development of oral tolerance: Concerns and controversiesPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2008Susan L. Prescott Rising rates of food allergies in early childhood reflect increasing failure of early immune tolerance mechanisms. There is mounting concern that the current recommended practice of delaying complementary foods until 6 months of age may increase, rather than decrease, the risk of immune disorders. Tolerance to food allergens appears to be driven by regular, early exposure to these proteins during a ,critical early window' of development. Although the timing of this window is not clear in humans, current evidence suggests that this is most likely to be between 4 and 6 months of life and that delayed exposure beyond this period may increase the risk of food allergy, coeliac disease and islet cell autoimmunity. There is also evidence that other factors such as favourable colonization and continued breastfeeding promote tolerance and have protective effects during this period when complementary feeding is initiated. This discussion paper explores the basis for concern over the current recommendation to delay complementary foods as an approach to preventing allergic disease. It will also examine the growing case for introducing complementary foods from around 4 months of age and maintaining breastfeeding during this early feeding period, for at least 6 months if possible. [source] Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cellsARTHRITIS & RHEUMATISM, Issue 4 2009Manuel A. González Objective Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Adult mesenchymal stem cells (MSCs) were recently found to suppress effector T cell responses and to have beneficial effects in various immune disorders. The purpose of this study was to examine a new therapeutic strategy for RA based on the administration of human adipose-derived MSCs (AD-MSCs). Methods DBA/1 mice with collagen-induced arthritis were treated with human AD-MSCs after disease onset, and clinical scores were determined. Inflammatory response was determined by measuring the levels of different mediators of inflammation in the joints and serum. The Th1-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with the autoantigen. The number of Treg cells and the suppressive capacity on self-reactive Th1 cells were also determined. Results Systemic infusion of human AD-MSCs significantly reduced the incidence and severity of experimental arthritis. This therapeutic effect was mediated by down-regulating the 2 deleterious disease components: the Th1-driven autoimmune and inflammatory responses. Human AD-MSCs decreased the production of various inflammatory cytokines and chemokines, decreased antigen-specific Th1/Th17 cell expansion, and induced the production of antiinflammatory interleukin-10 in lymph nodes and joints. Human AD-MSCs also induced de novo generation of antigen-specific CD4+CD25+FoxP3+ Treg cells with the capacity to suppress self-reactive T effector responses. Conclusion Human AD-MSCs emerge as key regulators of immune tolerance by inducing the generation/activation of Treg cells and are thus attractive candidates for a cell-based therapy for RA. [source] 4142: The Sanger Mouse Genetics Programme: high throughput characterisation of knockout miceACTA OPHTHALMOLOGICA, Issue 2010AK GERDIN Purpose The Sanger Mouse Genetics Programme (MGP) aims to make a significant impact on our understanding of the function of genes and their role in disease by generating, characterising and archiving in the order of 200 lines of knockout mice per year, including 40 lines as part of the EUMODIC consortium. The phenotyping screens employed include a wide range of assays relevant to key disease areas including diabetes, obesity, hearing and vision disorders, immune disorders, pain and motor function. The data generated by the primary screen will help to further the understanding of the interplay of genes and disease and will provide an insight into the various underlying biological pathways. All phenotyping data and biological resources generated by the programme are openly available to the scientific community. Methods Eye morphology is routinely assessed using the Slit Lamp and Ophthalmoscope and images are collected when abnormalities are identified. Expression profiling via the lacZ reporter gene is performed for each mutant line in adults and at E14.5. Results To date, the eye screen has been performed on over 180 mutant lines. Here we report examples of novel eye-related abnormalities identified by the eye morphology, embryonic lethality and/or expression screens performed by the Sanger MGP. We will present how to identify a potentially interesting mouse mutant on our database and discuss the impact our knock-out mouse models might have on your research. [source] Mannose binding lectin gene polymorphisms and asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2007X. Wang Summary Background Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. Subjects and method To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. Results Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47±0.07(SE) mg/L for asthmatics and 1.66±0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. Conclusion Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype. [source] | ||||||||||||||||||||||