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Th17 Responses (th17 + response)
Selected AbstractsIL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistanceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007Teresa Zelante Abstract Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL-23/IL-17 developmental pathway acted as a negative regulator of the Th1-mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL-23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter-regulating IL-12p70 production. Both IL-23 and IL-17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL-23/IL-17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi. See accompanying commentary: http://dx.doi.org/10.1002/eji.200737804 [source] Mapping immune response profiles: The emerging scenario from helminth immunologyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2007Alvaro Díaz Abstract Metazoan parasites of mammals (helminths) belong to highly divergent animal groups and yet induce a stereotypical host response: Th2-type immunity. It has long been debated whether this response benefits the host or the parasite. We review the current literature and suggest that Th2 immunity is an evolutionarily appropriate response to metazoan invaders both in terms of controlling parasites and repairing the damage they inflict. However, successful parasites induce regulatory responses, which become superimposed with, and control, Th2 responses. Beyond helminth infection, this superimposition of response profiles may be the norm: both Th1 and Th2 responses coexist with regulatory responses or, on the contrary, with the inflammatory Th17 responses. Thus, typical responses to helminth infections may differ from Th2-dominated allergic reactions in featuring not only a stronger regulatory component but also a weaker Th17 component. The similarity of immune response profiles to phylogenetically distinct helminths probably arises from mammalian evolution having hard-wired diverse worm molecules, plus tissue-damage signals, to the beneficial Th2 response, and from the convergent evolution of different helminths to elicit regulatory responses. We speculate that initiation of both Th2 and regulatory responses involves combinatorial signaling, whereby TLR-mediated signals are modulated by signals from other innate receptors, including lectins. [source] T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosisIMMUNOLOGY, Issue 2 2008Chris J. Hedegaard Summary Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and related the patient responses to disease activity, as indicated by magnetic resonance imaging. The MBP induced a dose-dependent release of interferon-, (IFN-,), tumour necrosis factor-, (TNF-,) and interleukin-10 (IL-10) by patient-derived MNCs. The patients' cells produced higher amounts of IFN-, and TNF-,, and lower amounts of IL-10, than cells from healthy controls (P < 0·03 to P < 0·04). Five patients with MS and no controls, displayed MBP-induced CD4+ T-cell proliferation. These high-responders exhibited enhanced production of IL-17, IFN-,, IL-5 and IL-4 upon challenge with MBP, as compared with the remaining patients and the healthy controls (P < 0·002 to P < 0·01). A strong correlation was found between the MBP-induced CD4+ T-cell proliferation and production of IL-17, IFN-,, IL-5 and IL-4 (P < 0·0001 to P < 0·01) within the patient group, and the production of IL-17 and IL-5 correlated with the number of active plaques on magnetic resonance images (P = 0·04 and P = 0·007). These data suggest that autoantigen-driven CD4+ T-cell proliferation and release of IL-17 and IL-5 may be associated with disease activity. Larger studies are needed to confirm this. [source] Late Crohn's disease patients present an increase in peripheral Th17 cells and cytokine production compared with early patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010M. VENY Aliment Pharmacol Ther,31, 561,572 Summary Background, Th1 and Th17 cells have been implicated in Crohn's disease (CD) pathophysiology and may play a role in disease persistence. Aim, To determine Th1 and Th17 responses in intestine and peripheral blood of early (<32 weeks since initial symptoms) and late (>2 years) CD patients. Methods, Cytokine mRNA in intestinal biopsies was determined by RT-PCR. Cytokine concentration in culture was measured by ELISA and cytokine-producing cells were identified by intracellular staining. Results, The inflamed mucosa showed significantly increased IL-17 mRNA levels compared with non-inflamed areas, both in early and late CD patients. However, only patients with late (n = 12), but not early (n = 9), active disease showed increased IL-17 production, as well as a significantly higher percentage of IL-17+CD4+ cells in blood, compared with controls (n = 12) or patients in remission (n = 13). Moreover, cultured peripheral CD4+ cells from late active CD patients presented significantly higher percentages of IL-17+, IL-22+ and IFN-,+ and a significantly increased production of IL-17 and IL-22, but not IFN-,+. Conclusions, Increased IL-17 gene transcription is common to early and late CD mucosa. However, exacerbated Th17 responses in the peripheral blood appear only in late disease. We propose that this population may constitute a mechanism of perpetuating the disease. [source] Granuloma formation in ANCA-associated vasculitidesAPMIS, Issue 2009PETER LAMPRECHT Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg,Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing ,NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity. [source] Excessive interleukin-1 signaling determines the development of Th1 and Th17 responses in chronic inflammationARTHRITIS & RHEUMATISM, Issue 2 2010Leo A. B. Joosten No abstract is available for this article. [source] Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloid cell,specific interleukin-1 receptor antagonistARTHRITIS & RHEUMATISM, Issue 2 2010Céline Lamacchia Objective The balance between interleukin-1 (IL-1) and its specific inhibitor, the IL-1 receptor antagonist (IL-1Ra), plays a major role in the development of arthritis. The purpose of this study was to investigate the role of IL-1Ra produced specifically by myeloid cells in the control of collagen-induced arthritis (CIA) by using myeloid cell,specific IL-1Ra,deficient mice (IL-1Ra,M). Methods IL-1Ra,M mice were generated by using the loxP/Cre recombinase system. CIA was induced in IL-1Ra,M mice and littermate control mice by a single immunization with bovine type II collagen (CII) in Freund's complete adjuvant. Arthritis severity was assessed by clinical and histologic scoring. Draining lymph node (DLN) cell responses were examined ex vivo, and ankle extracts were used in the quantification of cytokines and chemokines. Results Clinical and histopathologic evaluations revealed an early disease onset and a severe form of CIA in IL-1Ra,M mice. This was characterized by increased production of interferon-, (IFN,) and IL-17 by CII-stimulated DLN cells. We also observed that the CII-specific CD4+ T cell response shifted in vivo, from a dominant Th1 response early in the course of the arthritis to the presence of both Th1 and Th17 cytokines later in the disease course. Interestingly, IL-1Ra levels were higher in the arthritic joints of IL-1Ra,M mice as compared with the controls, indicating that nonmyeloid cells strongly contribute to the local production of IL-1Ra. However, this enhanced IL-1Ra production was not sufficient to limit joint inflammation and tissue damage. Conclusion Our results suggest that myeloid cell,derived IL-1Ra plays a critical role in the control of the development and the severity of CIA by modulating Th1 and Th17 responses in lymphoid organs. [source] | ||||||||||