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: 3.04). 09/2009; 157(2):209-15. DOI: 10.1111/j.1365-2249.2009.03944.x
Source: PubMed


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.

Download full-text


Available from: Jose C Crispin
  • Source
    • "SLE is a complex autoimmune disorder characterized by autoantibody and immune complex formation and has has been strongly correlated to a dysregulated Th17/regulatory T cell balance [194, 195]. IL-17 and Th17 cells have been detected at higher levels in several murine models of lupus compared to those found in healthy, wild type mice [196]. A role for Th17 cells in murine lupus was demonstrated with the success of an anti-CD3 antibody in symptom improvement whose effects were dependent on decreased IL-17 production and a decrease in Th17 kidney-infiltrating cells; tolerance was correlated with decreased levels of IL-6 production but an increase in TGFβ and regulatory T cells [197]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression.
    Full-text · Article · Dec 2013 · Clinical and Developmental Immunology
  • Source
    • "Indeed, one of the BAFF receptors, BAFF-receptor (BAFF-R or BR3) is expressed on activated T cells and Tregs (reviewed in Vincent et al. [2]). Dong et al. has shown that IL-17 increased IL-6 and anti-dsDNA antibodies in supernatant of culture PBMCs from lupus nephritis patients [48], suggesting a role for IL-17 in human B cell activation [8]. Supporting this, Hsu et al., showed that autoimmune BXD2 mice, which spontaneously produce high IL-17 levels, develop less germinal centre B cells as well as reduced humoral responses when IL-17R is lacking [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Serum interleukin (IL)-17 concentrations have been reported to be increased in systemic lupus erythematosus (SLE), but associations with clinical characteristics are not well understood. We characterized clinical associations of serum IL-17 in SLE. We quantified IL-17 in serum samples from 98 SLE patients studied cross-sectionally, and in 246 samples from 75 of these patients followed longitudinally over two years. Disease activity was recorded using SLE Disease Activity Index (SLEDAI)-2k. Serum IL-6, migration inhibitory factor (MIF), and B cell activating factor from the tumour necrosis factor family (BAFF) were also measured in these samples. Serum IL-17 levels were significantly higher in SLE patients compared to healthy donors (P<0.0001). No correlation was observed between serum IL-17 and SLEDAI-2k, at baseline or during longitudinal follow-up. However, we observed that SLEDAI-2k was positively correlated with IL-17/IL-6 ratio. Serum IL-17 was significantly increased in SLE patients with central nervous system (CNS) disease (P=0.0298). A strong correlation was observed between serum IL-17 and IL-6 (r=0.62, P<0.0001), and this relationship was observed regardless of disease activity and persisted when integrating cytokine levels over the period observed (r=0.66, P<0.0001). A strong correlation of serum IL-17 was also observed with serum BAFF (r=0.64, P<0.0001), and MIF (r=0.36, P=0.0016). Serum IL-17 concentration correlates poorly with SLE disease activity, but is significantly elevated in patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6 alone to characterize Th17-driven disease, such as SLE. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE.
    Full-text · Article · Aug 2013 · Arthritis research & therapy
  • Source
    • "However, there is increasing evidence that T cells have a major place in SLE mechanisms. In this context, the role of Th17 cells during SLE has recently become subject of increasing attention [155]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past decades, the identification of several new cytokines, including interleukin (IL)-17 and IL-23, and of new T helper cell subsets, including Th17 cells, has changed the vision of immunological processes. The IL-17/Th17 pathway plays a critical role during the development of inflammation and autoimmunity, and targeting this pathway has become an attractive strategy for a number of diseases. This review aims to describe the effects of IL-17 in the joint and its roles in the development of autoimmune and inflammatory arthritis. Furthermore, biotherapies targeting directly or indirectly IL-17 in inflammatory rheumatisms will be developed.
    Full-text · Article · Jul 2013
Show more