Th9 cells and IL-9 in autoimmune disorders: Pathogenesis and therapeutic potentials

Deng, Yaxiong; Wang, Zijun; Chang, Christopher; Lü, Lei; Lau, Chak Sing; Lu, Qianjin

doi:10.1016/j.humimm.2016.12.010

Cited by 81 publications

(55 citation statements)

References 79 publications

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“…In addition, we have shown that mannan conjugation of self-MBP, PLP or MOG native peptides or altered peptide ligands, are able to divert Th1 responses to Th2 responses in human PBMC from MS patients, in immunized mouse spleen cells and are able to ameliorate EAE in mice [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73]. The role of Th9 cells in MS is not as clear although in mice, IL-9 and Th9 cells induce EAE and inflammation and IL-9 knockout mice are protected from developing EAE [74]. Th17 cells play a crucial role in the pathogenesis of MS in both mice and humans by inducing an inflammatory milieu.…”

Section: T Helper Cellsmentioning

confidence: 99%

Multiple Sclerosis: Immunopathology and Treatment Update

et al. 2017

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The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.

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Section: T Helper Cellsmentioning

confidence: 99%

Multiple Sclerosis: Immunopathology and Treatment Update

et al. 2017

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“…Helper T (CD4 + ) cells preferentially producing interleukin (IL)-9 have recently been described as distinct Th9 cells and implicated in several inflammatory conditions such as infectious, neoplastic and autoimmune diseases [ 1 – 4 ]. Contribution of these cells in the pathogenesis of autoimmunity has been demonstrated in animal studies of colitis [ 5 , 6 ], uveitis [ 7 ], and experimental autoimmune encephalomyelitis (EAE) [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis

et al. 2018

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BackgroundRole of Th9 cells and interleukin-9 (IL-9) in human autoimmune diseases such as psoriasis and ulcerative colitis has been explored only very recently. However, their involvement in human rheumatoid arthritis (RA) is not conclusive. Pathogenesis of RA is complex and involves various T cell subsets and neutrophils. Here, we aimed at understanding the impact of IL-9 on infiltrating immune cells and their eventual role in synovial inflammation in RA.MethodsIn vitro stimulation of T cells was performed by engagement of anti-CD3 and anti-CD28 monoclonal antibodies. Flow cytometry was employed for measuring intracellular cytokine, RORγt in T cells, evaluating apoptosis of neutrophils. ELISA was used for measuring soluble cytokine, Western blot analysis and confocal microscopy were used for STAT3 phosphorylation and nuclear translocation.ResultsWe demonstrated synovial enrichment of Th9 cells and their positive correlation with disease activity (DAS28-ESR) in RA. Synovial IL-9 prolonged the survival of neutrophils, increased their matrix metalloprotienase-9 production and facilitated Th17 cell differentiation evidenced by induction of transcription factor RORγt and STAT3 phosphorylation. IL-9 also augmented the function of IFN-γ + and TNF-α + synovial T cells.ConclusionsWe provide evidences for critical role of IL-9 in disease pathogenesis and propose that targeting IL-9 may be an effective strategy to ameliorate synovial inflammation in RA. Inhibiting IL-9 may have wider impact on the production of pathogenic cytokines involved in autoimmune diseases including RA and may offer better control over the disease.Electronic supplementary materialThe online version of this article (10.1186/s13075-017-1505-8) contains supplementary material, which is available to authorized users.

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“…The gene is located in 5q31.1 . IL‐9 production requires signal induction from both TGF‐β and IL‐4 or from IL‐25 while many parallel pathways are implied . Its main function consists of inhibiting T H 1 response and stimulating IgE release .…”

Section: Resultsmentioning

confidence: 99%

The role of interleukins in preeclampsia: A comprehensive review

Bellos

Karageorgiou

Kapnias

et al. 2018

American J Rep Immunol

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Preeclampsia is a multi‐system hypertensive disorder of pregnancy, with significant rates of maternal and neonatal morbidity. It represents a major cause of preterm birth, as definitive treatment demands fetal delivery. Although its pathophysiology is complicated, placental hypoxia and endothelial dysfunction constitute established pathogenetic steps of the disease. Inflammation is considered to be a crucial mediator of preeclampsia process, as an imbalance between TH1, TH2, and TH17 immune responses is observed. The present review accumulates current knowledge about the contribution of interleukins in preeclampsia, summarizing the pathways through which each interleukin exerts its function in the disease. Also, the role of genetic polymorphisms is explored and the predictive efficacy of maternal serum interleukin levels is evaluated. Finally, recommendations about the safe interpretation of the outcomes, as well as guidance for future research, are provided.

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Th9 cells and IL-9 in autoimmune disorders: Pathogenesis and therapeutic potentials

Cited by 81 publications

References 79 publications

Multiple Sclerosis: Immunopathology and Treatment Update

Multiple Sclerosis: Immunopathology and Treatment Update

Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis

The role of interleukins in preeclampsia: A comprehensive review

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