Th 9 cells in Behçet disease: Possible involvement of IL-9 in pulmonary manifestations

Kaabachi, Wajih; Khaouthar, Mnasria; Hamdi, Besma; Khalfallah, I.; Ammar, Jamel; Hamzaoui, Kamel; Hamzaoui, A.

doi:10.1016/j.imlet.2019.05.004

Cited by 9 publications

(4 citation statements)

References 45 publications

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“… 69 , 70 , 71 Similarly, Behçet's disease has been associated with high concentrations of both soluble ST2 and IL-33, as well as increased CXCL10 and CCL2, Vγ9Vδ2 T-cell expansion, IL-17F gene polymorphisms, and intense recruitment of T cells producing IL-9 and IL-17 to the lungs. 72 , 73 , 74 , 75 , 76 Some patients with either Behçet's disease 77 or COVID-19 78 also show positivity for antiphospholipid antibodies, which might further contribute to the coagulopathy seen in both conditions.…”

Section: Similarities Between Covid-19 Kawasaki Disease and Behçet'mentioning

confidence: 99%

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

Zizzo

Cohen

2020

The Lancet Rheumatology

104

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The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild-moderate, severe-critical, and chronic-fibrotic). In susceptible individ uals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33-ST2 axis might act to expand the number of pathogenic granulocyte-macrophage colony-stimulating factorexpressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelialmesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.

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Section: Similarities Between Covid-19 Kawasaki Disease and Behçet'mentioning

confidence: 99%

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

Zizzo

Cohen

2020

The Lancet Rheumatology

104

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“…In alignment with these findings, a study investigating Behcet’s disease reported a favorable association between increased serum IL-9 levels and IL-17 ( 42 ). Furthermore, an augmented presence of Th9 cells and elevated plasma IL-9 levels in patients with active immune thrombocytopenia exhibited positive correlations with Th17 cells and IL-17 levels, respectively ( 43 ).…”

Section: Discussionmentioning

confidence: 75%

Increased interleukin-9 and Th9 cells in patients with refractory Graves’ disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases

Yao,

Song,

Wang

et al. 2024

Front. Immunol.

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IntroductionAutoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited. MethodsWe investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs.ResultsWe reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08).DiscussionOur results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.

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“…TSLP forms a new dimer after binding with TSLPR and IL-7R on the surface of dendritic cells, promotes JAK1 and JAK2 phosphorylation, further leads to STAT5 phosphorylation, and then plays its biological role ( Yao et al, 2013 ; Liao et al, 2014 ; Olson et al, 2016 ). Further research on dendritic cells showed that dendritic cells expressed OX40L after being stimulated by TSLP and combined with the OX40 of primitive CD4 + T cells to play a role, resulting in the increase of Th2 cell differentiation ( Garo et al, 2017 ; Kaabachi et al, 2019 ). The TSLP pathway can promote the transformation of primitive naive CD4 + T cells in lymph nodes into Th2 cells ( Qiao et al, 2014 ), which explains the polarization of Th2.…”

Section: Discussionmentioning

confidence: 99%

IL-9 neutralizing antibody suppresses allergic inflammation in ovalbumin-induced allergic rhinitis mouse model

Zhao

Wang

et al. 2022

Front. Pharmacol.

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Allergic rhinitis is mainly mediated by IgE after specific individuals are exposed to allergens. It is a common nasal mucosa disease of non-infectious chronic inflammatory disease and is often accompanied by asthma and conjunctivitis. In the study of allergic asthma, it was found that IL-9 participates in the pathogenic development of asthma. Because asthma and allergic rhinitis have the same airway and the same disease, it is inferred that IL-9 may also play an important role in allergic rhinitis. BALB/c mice received intranasal stimulation of ovalbumin (OVA) treatment at different times. The nasal mucosa of the mice were then sliced and stained with Sirius red and Toluidine blue, and eosinophils and mast cells in the mucosa were counted. ELISA was used to detect the expression of OVA-IgE in peripheral blood. The Th2 cell fraction in the mouse spleen was detected by flow cytometry. The expressions of IL-4, IL-5, IL-9, and IL-13 and their mRNA in mucosa were detected by real-time PCR and flow cytometry bead array analysis. Finally, the expression changes of Thymic stromal lymphopoietin related proteins and its mRNA, JAK1/2, and STAT5 proteins were detected by real-time PCR and Western blot. After the intervention with the IL-9 neutralizing antibody, the symptoms of allergic rhinitis in mice were significantly reduced. The expression of OVA-IgE in the peripheral blood of mice was inhibited, the fraction of Th2 cells in the spleen decreased, the related cytokines (IL-4, IL-5, and IL-13) were inhibited, and their functions decreased. The TSLP-OX40/OX40L signal pathway and JAK1/2-STAT5 signal are inhibited. IL-9 neutralizing antibody has a good therapeutic effect on the mouse model of allergic rhinitis, which may be related to the TSLP-OX40/OX40L pathway and JAK1/2-STAT5 signaling.

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Th 9 cells in Behçet disease: Possible involvement of IL-9 in pulmonary manifestations

Cited by 9 publications

References 45 publications

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

Increased interleukin-9 and Th9 cells in patients with refractory Graves’ disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases

IL-9 neutralizing antibody suppresses allergic inflammation in ovalbumin-induced allergic rhinitis mouse model

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