Interleukin-17 and systemic lupus erythematosus: current concepts.

Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Clinical & Experimental Immunology (Impact Factor: 3.41). 09/2009; 157(2):209-15. DOI: 10.1111/j.1365-2249.2009.03944.x
Source: PubMed

ABSTRACT The emerging role of interleukin (IL)-17 as a hallmark proinflammatory cytokine of the adaptive immune system, produced primarily by a new T helper cell subset termed 'Th17', has received considerable attention. Differentiation of Th17 cells is driven by the simultaneous presence of transforming growth factor-beta and certain inflammatory cytokines (e.g. IL-6, IL-21), and recent studies have shown that inflammation instigated by IL-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. In this review, we focus on the information regarding IL-17 and systemic lupus erythematosus (SLE), a chronic autoimmune disease. The work that has explored the development and behaviour of IL-17-producing cells in SLE is discussed, and different mechanisms by which IL-17 could potentially augment inflammation and autoantibody production in the context of SLE are proposed.

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    ABSTRACT: Growing evidence suggests that IL-17-producing T cells, lacking both CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal role in the pathogenesis of a number of systemic autoimmune disorders. We recently demonstrated that this T-cell subset is expanded in the peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS), produces IL-17 and accumulates in minor salivary glands (MSGs). We aimed to investigate glandular and PB DN T cells in early pSS in order to verify a possible correlation with MSGs histological patterns and clinical parameters. Paired samples of PB mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by flow cytometry and immunofluorescence staining respectively. Histological analysis to identify histological scores, B/T cell segregation and the presence of germinal center (GC)-like structures was also performed. In early stages of pSS, circulating DN T cells appear to be not yet expanded and inversely correlated with circulating CD4(+)Th17 cells. The number of infiltrating DN T cells were associated with extent of glandular involvement, presence of GC-like structures and dryness symptoms and were inversely correlated with circulating DN T cells. Our findings suggest that DN T cells are actively involved in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS and may play a role in ectopic lymphoneogenesis development occurring during the disease.
    Journal of Autoimmunity 01/2014; · 8.15 Impact Factor
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    ABSTRACT: The TH17 lineage of T cells and its canonical cytokine IL-17 have been the focus of many recent studies in autoimmune, allergic, and infectious disease. In this review, we will briefly discuss the current knowledge about the role of these cells and IL-17 in a spectrum of disorders. It is clear that IL-17 plays pathogenic roles in certain conditions while the same pathway is critically important to immunity in others. Targeting of TH17 cells or IL-17 therapeutically may impart many benefits, but this approach is not without potentially serious implications regarding host defense. These issues will be discussed herein as we evaluate pharmacological approaches targeting this pathway that are just beginning to be fully tested in human disease.
    Current Allergy and Asthma Reports 06/2013; · 2.75 Impact Factor
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    ABSTRACT: OBJECTIVES: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients. METHODS: Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients. RESULTS: We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine. CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication.
    Clinics (São Paulo, Brazil) 06/2013; 68(6). · 1.59 Impact Factor

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