Associations between serum interleukin-23 levels and clinical characteristics in patients with systemic lupus erythematosus

Du, Juan; Li, Zongshu; Shi, Jingwei; Bi, Liqi

doi:10.1177/0300060513509130

Cited by 21 publications

(20 citation statements)

References 27 publications

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“…A number of studies have indicated that the level of IL-12, IL-23, IL-27, and IL-35 is increased in the plasma of SLE patients compared with healthy controls [28][29][30][31][32]. Furthermore, IL-27 or IL-35 has also been shown to suppress lupus flare and nephritis in the MRL/lpr mice, suggesting that IL-27 and IL-35 may be therapeutically relevant in SLE [33,34].…”

Section: Discussionmentioning

confidence: 99%

A novel IL‐23p19/Ebi3 (IL‐39) cytokine mediates inflammation in Lupus‐like mice

et al. 2016

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Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27sue injury by promoting the expansion of regulatory B and T-cell subsets [2,3].Discovery of IL-23 in 2000 [4] led to the reevaluation of IL-12 and IL-23 in autoimmune diseases. For example, therapeutic targeting of IL-12p40 decreases pathology in many mouse models of autoimmune diseases [5], while disease is exacerbated in IL-12p35-deficient mice [6,7]. Thus, IL-23 rather than IL-12 was * These authors contributed equally to this work as first authors.* * These authors contributed equally to this work as senior authors. Eur. J. Immunol. 2016. 46: 1343-1350 found to be the critical cytokine for autoimmune inflammation including experimental immune-mediated disease [6][7][8][9][10]. Currently, at least ten therapeutic agents targeting IL-23 are being tested in the clinic for more than 17 human immune-mediated diseases [11]. Both IL-27 and IL-35 have immune-suppressive activities and are also cytokines with strikingly diverse influences on the immune response so that viable therapeutic targets may also be exploited for treatment of human inflammatory diseases [12,13]. Thus, understanding immunobiology of IL-12 family cytokines would undoubtedly provide valuable knowledge that can be exploited therapeutically. The IL-12 family cytokines are α/β heterodimers consisting of one α subunit (IL-23p19, IL-27p28, IL-12p35) and one β chain (IL-12p40, Ebi3) [14,15]. Although there are currently four known members in the family, the predictable range of combinations is six and it is conceivable that additional pairings such as IL-23p19/Ebi3 are possible [12,[14][15][16][17]. In this study, we sought to discover additional IL-12 members that might exist in nature. By combining different alpha and beta IL-12 subunit proteins in vitro we detected a novel stable p19/Ebi3 heterodimeric complex by immunoprecipitation. We have characterized the p19/Ebi3 cytokine (IL-39) and demonstrated that it possesses biological activities in vitro and in vivo. Results IL-23p19 (p19) and Ebi3 form a composite factor (IL-39)To examine whether p19 can form a stable complex with Ebi3, we mixed equal amounts of the two proteins and immunoprecipitation (IP)/Western blot analyses revealed formation of a stable human p19/Ebi3 complex (Fig. 1A). We could not detect the p19/Ebi3 following IP with isotype IgG or anti-c-Jun antibody, providing suggestive evidence for potential bona fide p19/Ebi3 cytokine. To confirm our finding in another animal species, we genetically engineered and expressed mouse p19 and Ebi3 subunits in CHO cells (Fig. 1B). IP of supernatants derived from transfectants with anti-p19 mAb and followed by Western blot analysis using anti-Ebi3 mAb confirmed coexpression p19 and Ebi3 and formation of a stable p19/Ebi3 heterodimer (Fig. 1C). We further confirmed this observation by reciprocal IP with anti-Ebi3 mAb and Western blotting with anti-p19 mAb and the p19/Ebi3 comple...

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Section: Discussionmentioning

confidence: 99%

A novel IL‐23p19/Ebi3 (IL‐39) cytokine mediates inflammation in Lupus‐like mice

et al. 2016

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“…Also IL-23, which is one of the main cytokines responsible for development, expansion, and proliferation of Th17 cells, plays an important role in pathogenesis of SLE. Du et al ( 2014 ) showed that the level of IL-23 was elevated in patients with SLE. They also demonstrated the correlation between the increased level of IL-23 and renal disease in SLE.…”

Section: The Role Of Th17 Cells and Related Cytokines In Pathogenesismentioning

confidence: 99%

“…Kyttaris et al ( 2010 ) observed that IL-23R deficiency prevented the development of nephritis in lupus-prone mice. Therefore, IL-23 is considered to be a potential biomarker for renal involvement in SLE and a potential therapeutic target (Du et al 2014 ).…”

Section: The Role Of Th17 Cells and Related Cytokines In Pathogenesismentioning

confidence: 99%

The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases

Tabarkiewicz

Pogoda

Karczmarczyk

et al. 2015

Arch. Immunol. Ther. Exp.

202

126

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The end of twentieth century has introduced some changes into T helper (Th) cells division. The identification of the new subpopulation of T helper cells producing IL-17 modified model of Th1–Th2 paradigm and it was named Th17. High abilities to stimulate acute and chronic inflammation made these cells ideal candidate for crucial player in development of autoimmune disorders. Numerous publications based on animal and human models confirmed their pivotal role in pathogenesis of human systemic and organ-specific autoimmune diseases. These findings made Th17 cells and pathways regulating their development and function a good target for therapy. Therapies based on inhibition of Th17-dependent pathways are associated with clinical benefits, but on the other hand are frequently inducing adverse effects. In this review, we attempt to summarize researches focused on the importance of Th17 cells in development of human autoimmune diseases as well as effectiveness of targeting IL-17 and its pathways in pre-clinical and clinical studies.

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“…В биоптатах почек у пациентов с волча-ночным нефритом обнаружена инфильтрация Th17-клетками [108,109], а концентрация ИЛ17 в почечной ткани коррелирует с выраженностью микрогематурии, протеинурии, сывороточным уровнем мочевины и кли-нической активностью СКВ [110]. Наряду с ИЛ17, в сы-воротках пациентов с СКВ наблюдается увеличение кон-центрации ИЛ23 [111,112]. Установлено, что гиперэкс-прессия ИЛ23 обусловлена увеличением связывания ИФН-регуляторного фактора 3 и промотерного участка ИЛ23р19 [113].…”

Section: болезнь бехчетаunclassified

New Possibilities of Pharmacotherapy for Immunoinflammatory Rheumatic Diseases: A Focus on Inhibitors of Interleukin-17

Насонов¹

2017

rsp

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Associations between serum interleukin-23 levels and clinical characteristics in patients with systemic lupus erythematosus

Cited by 21 publications

References 27 publications

A novel IL‐23p19/Ebi3 (IL‐39) cytokine mediates inflammation in Lupus‐like mice

A novel IL‐23p19/Ebi3 (IL‐39) cytokine mediates inflammation in Lupus‐like mice

The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases

New Possibilities of Pharmacotherapy for Immunoinflammatory Rheumatic Diseases: A Focus on Inhibitors of Interleukin-17

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