Immune-mediated experimental arthritis in IL-33 deficient mice

Talabot-Ayer, Dominique; Martin, Praxedis; Seemayer, Christian A.; Vigne, Solenne; Lamacchia, Céline; Finckh, Axel; Saïji, Essia; Gabay, Cem; Palmer, Gaby

doi:10.1016/j.cyto.2014.05.007

Cited by 16 publications

(13 citation statements)

References 29 publications

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“…This finding suggested a pathogenic role for IL-33, signaling through ST2L, in these experimental models (20)(21)(22). However, although arthritis is reduced in ST2 KO mice, it did not differ in IL-33 KO mice compared with wild-type mice (25,26). One hypothesis of this striking contrast could be that ST2L can cross-activate other signaling pathways in addition to IL-33-mediated signals (53).…”

Section: Discussionmentioning

confidence: 42%

“…IL-33 synergistically enhances immune complex-induced TNF-a and IL-8 production in cultured human synovium-derived mast cells (21). In mouse models, whereas arthritis is reduced in ST2 knockout (KO) or in anti-ST2-treated mice x Institut de Pharmacologie et de Biologie Structurale CNRS-Université de Toulouse III, F-31000 Toulouse, France; and (22)(23)(24), it does not differ in IL-33 KO mice compared with wild-type mice (25,26). These studies in arthritis models underscore the complex nature of IL-33 and the necessity to establish how administered IL-33 modulates the inflammatory and regulatory pathways, respectively, involved in arthritis control.…”

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confidence: 99%

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In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

Biton

Athari

Thiolat

et al. 2016

The Journal of Immunology

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IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33–treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33–treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39high Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development.

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Section: Discussionmentioning

confidence: 42%

mentioning

confidence: 99%

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

Biton

Athari

Thiolat

et al. 2016

The Journal of Immunology

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“…In patients with RA, biomarker studies have suggested that the serum level of IL-33 could reflect clinical activity [12] and disease severity, or predict carotid plaque progression [13]. However, the role of IL-33 could be paradoxical since, in K/BxN serum transfer-induced arthritis, ST2 but not IL-33 blockade may improve arthritis [14, 15]. Moreover, IL-33-stimulated mast cells could also suppress monocyte activation [16] and intracellular IL-33 also has anti-osteoclastogenic and anti-inflammatory properties [11].…”

Section: Introductionmentioning

confidence: 99%

Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis

et al. 2016

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BackgroundRecent works have suggested a possible link between interleukin (IL)-33 and B-cell biology. We aimed to study the possible association between serum IL-33 detection and response to rituximab (RTX) in rheumatoid arthritis (RA) patients in different cohorts with an accurate enzyme-linked immunosorbent assay (ELISA).MethodsSerum IL-33, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and high serum immunoglobulin (Ig)G levels were assessed in 111 RA patients receiving a first course of 2 g RTX (cohort 1) in an observational study and in 74 RA patients treated with the same schedule in routine care (cohort 2). Univariate and multivariate analyses identified factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.ResultsAt week 24, 84/111 (76%) and 54/74 (73%) patients reached EULAR response in cohorts 1 and 2, respectively. Serum IL-33 was detectable in only 33.5% of the patients. In the combined cohorts, the presence of RF or anti-CCP (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.13–9.46; p = 0.03), high serum IgG (OR 2.32, 95% CI 1.01–5.33; p = 0.048), and detectable serum IL-33 (OR 2.40, 95% CI 1.01–5.72; p = 0.047) were all associated with RTX response in multivariate analysis. The combination of these three factors increased the likelihood of response to RTX. When serum IL-33 detection was added to seropositivity and serum IgG level, 100% of the patients with the three risk factors (corresponding to 9% of the population) responded to RTX (OR versus patients with none of the three risk factors 29.61, 95% CI 1.30–674.79; p = 0.034).ConclusionDetectable serum IL-33 may predict clinical response to RTX independently of, and synergistically with, auto-antibodies and serum IgG level.Trial registration NCT01126541; 18 May 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1190-z) contains supplementary material, which is available to authorized users.

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“…The potent role of IL-33 during arthritis was evidenced in previous studies; however, the genetic deficiency of IL-33 did not affect collagen-induced arthritis, 54 and anti-ST2 antibody treatment protected mice against collagen-induced arthritis. 55 In liver disease, the genetic ablation of IL-33 or ST2 sensitized the mice to develop enhanced ConA liver injury compared with WT mice.…”

Section: Beneficial Effects Of Blocking Il-33 or St2 In Different Dismentioning

confidence: 58%

Potential Therapeutic Aspects of Alarmin Cytokine Interleukin 33 or Its Inhibitors in Various Diseases

Arshad

Khan

Noel

et al. 2016

Clinical Therapeutics

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The protective or exacerbated aspects of use of IL-33 or its inhibitors are dependent on the type of infection or inflammatory condition, duration of disease (acute or chronic), organ involved, cytokine microenvironment, dose or kinetics of IL-33, and genetic predisposition. The alarmin cytokine IL-33 acts at cellular, molecular, and transcriptional levels to mediate pluripotent functions in various diseases and has potential therapeutic value to mitigate the disease process.

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Immune-mediated experimental arthritis in IL-33 deficient mice

Cited by 16 publications

References 29 publications

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis

Potential Therapeutic Aspects of Alarmin Cytokine Interleukin 33 or Its Inhibitors in Various Diseases

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