The capacity of Th2 lymphocytes to deliver B‐cell help requires expression of the transcription factor STAT3

Mari, Nathalie; Hercor, Mélanie; Denanglaire, Sébastien; Léo, Oberdan; Andris, Fabienne

doi:10.1002/eji.201242938

Cited by 25 publications

(19 citation statements)

References 50 publications

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“…Indeed, Th17 cells, which are decreased by UA treatment, are known to play a role in antibody production [3] . These results are consistent with other known functions of STAT3, including the generation of follicular helper T cells [30] and development of Th2-mediated B cells [31] . Taken together, it is clear that UA ameliorates autoimmune arthritis by targeting multiple processes associated with STAT3 activation.…”

Section: Discussionsupporting

confidence: 91%

Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation

Baek

Lee

et al. 2014

Acta Pharmacol Sin

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Aim: Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and antioxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects. Methods: CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4 + IL-17 + , CD4 + CD25 + Foxp3 + and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4 + T cells and CD19 + B cells were purified from mice spleens for in vitro studies. Results: UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and RORγt in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19 + B cells pretreated with IL-21 or LPS in vitro. Conclusion: UA treatment significantly ameliorates CIA in mice via suppression of Th17 and differentiation. By targeting pathogenic Th17 cells and autoantibody production, UA may be useful for the treatment of autoimmune arthritis and other Th17-related diseases.

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Section: Discussionsupporting

confidence: 91%

Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation

Baek

Lee

et al. 2014

Acta Pharmacol Sin

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“…CD62L hi CD4 + T cells and B cells were purified from naive animals by magnetic separation, as previously described (16, 17). The percentage of purified cell fractions in all experiments ranged between 90 and 98%, as estimated by flow cytometry (data not shown).…”

Section: Methodsmentioning

confidence: 99%

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

et al. 2017

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Follicular helper T cells (Tfh) have been identified as the primary cell subpopulation regulating B cell responses in germinal centers, thus supporting high-affinity antibody production. Among the transcription factors orchestrating Tfh cell differentiation and function, the role played by the proto-oncogene c-Maf remains poorly characterized. We report herein that selective loss of c-Maf expression in the T cell compartment results in defective development of Tfh cells in response to both antigen/adjuvant vaccinations and commensal intestinal bacteria. Accordingly, c-Maf expression in T cells was essential for the development and high-affinity antibody secretion in vaccinated animals. c-Maf was expressed early, concomitantly to BCL6, in Tfh cell precursors and found to regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and the regulation of humoral immune responses to T-cell-dependent antigens.

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“…Although the activation of STAT3 was first described in Th1 lymphocytes (44), increasing evidence suggests that this pathway plays a major role in Th2 lymphocyte differentiation (45)(46)(47). The Wnt/b-catenin pathway also stimulates Th2 differentiation, as well as IL-4 and IL-13 production, in human CD4 + T cells in a mouse model of allergic asthma (48,49).…”

Section: Discussionmentioning

confidence: 99%

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

Morin

Kavian

Nicco

et al. 2016

The Journal of Immunology

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Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide. Skin and lung fibrosis as well as immunological features were studied. Mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1 autoantibodies. STAT3, AKT, and Wnt/β-catenin pathways were hyperactivated in the skin and the lungs of diseased mice. Niclosamide reversed fibrosis of the skin and the lungs. Beneficial immunological effects were also observed because niclosamide decreased the activation of CD4+ and CD8+ T cells, autoimmune B cell activation, as well as IL-4 and IL-13 production in the skin. The improvement permitted by niclosamide in the mouse model of HOCl-induced SSc as well as the well-documented safety profile of this drug provide a rationale for the evaluation of niclosamide in the management of patients affected by this disease.

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The capacity of Th2 lymphocytes to deliver B‐cell help requires expression of the transcription factor STAT3

Cited by 25 publications

References 50 publications

Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation

Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

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