Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: Implications for Th17-mediated inflammation in auto-immunity

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Clinical Immunology (Impact Factor: 3.67). 07/2008; 127(3):385-93. DOI: 10.1016/j.clim.2008.01.019
Source: PubMed


IL-23-dependent IL-17-producing T helper (Th) lymphocytes are associated with autoimmunity. We investigated the immunopathological mechanisms for activation of Th17 cells of patients with systemic lupus erythematosus (SLE). Concentration of cytokines/chemokine in plasma and culture supernatant from SLE patients and healthy controls were measured by ELISA or flow cytometry. Plasma IL-12, IL-17, IL-23 and CXCL10 concentrations and the number of Th17 cells were significantly elevated in SLE patients than control subjects (both p<0.05). Elevated IL-12, IL-17 and CXCL10 concentrations correlated positively and significantly with SLEDAI (all p<0.05). Plasma IL-12 and IL-17 showed significant and positive correlation with plasma Th1 chemokine CXCL10 concentration in SLE patients (all p<0.05). Ex vivo inductions of IL-17 by IL-23 or IL-18 from co-stimulated lymphocytes were significantly higher in SLE patients than controls (all p<0.05). The activated IL-23/IL-17 axis is important for the inflammatory immunity in SLE.

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    • "The role of Th17 cells in SLE has been supported by the higher serum levels of IL-17 [94, 95] and the higher frequency of circulating Th17 cells [95–97], although no differences between patients with the active and inactive forms of the disease has been found [93]. As has been reported for other diseases, the Treg/Th17 ratio was seen to be reduced in patients [96, 98]. "
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    ABSTRACT: The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review.
    Full-text · Article · Aug 2014
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    • "It has been proposed in SLE that DCs commonly come into contact with apoptotic debris and therefore develop into a mature phenotype and produce higher amounts of IL-6; in turn the higher level of IL-6 production results in the differentiation of naïve CD4+ T cells into Th17 cells, when in fact they may have been converted into regulatory T cells under normal conditions [199]. SLE patients have elevated levels of inflammatory cytokines including IL-23, IL-17, and IL-6 and higher frequencies of lymph nodal Th17 cells [200, 201]. SLE patients have also been found to have decreased absolute numbers of regulatory T cells, and it has been shown that higher numbers of regulatory T cells correlate to decreased disease severity [202]. "
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    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
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    • "IL-17 is recognized to have a central role in lupus-prone mouse models [9,10] and therefore presumed to be involved in human SLE pathogenesis (reviewed in Nalbandian et al. [8]). Although not observed in all studies [6], serum IL-17 levels have been found to be elevated in SLE patients compared to controls [11-13]. Correlations between serum IL-17 levels and SLE disease activity and anti-double stranded DNA (anti-dsDNA) antibody levels have previously been reported in some studies [11,13]. "
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    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
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