IL-9 and Th9 cells in health and diseases—From tolerance to immunopathology

Li, Junhui; Chen, Shuqiu; Xiang, Xiao; Zhao, Yong; Ding, Wenjun; Li, Xian Chang

doi:10.1016/j.cytogfr.2017.07.004

Cited by 77 publications

(54 citation statements)

References 78 publications

(142 reference statements)

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“…Our data also show that IL‐9 expression is increased in both PB CD4 + and CD8 + T cells from RA patients, and BM‐MSCs have the ability to hamper its production. Though IL‐9 has been classically linked to allergic inflammation (atopic dermatitis and asthma), recently, it has been shown to be implicated in antiparasitic immunity and in the pathogenesis of an array of autoimmune disorders, such as RA, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus (J. Li et al, ). It was recently described an increased percentage of PB Th9 cells in RA patients, which were specifically activated by citrullinated peptides.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Pedrosa

Gomes

Laranjeira

et al. 2019

J Tissue Eng Regen Med

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Rheumatoid arthritis (RA) is a Th1/Th17‐mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease‐modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)‐MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4+ and CD8+ T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM‐MSCs. The expression of (interleukin) IL‐2, tumor necrosis factor alpha (TNF‐α), and interferon‐gamma (IFN‐γ) was evaluated in naive, central memory, effector memory, and effector CD4+ and CD8+ T cells, whereas IL‐6, IL‐9, and IL‐17 expression was measured in total CD4+ and CD8+ T cells. mRNA expression of IL‐4, IL‐10, transforming growth factor beta (TGF‐β), cytotoxic T‐lymphocyte‐associated antigen 4, and/or forkhead box P3 was quantified in fluorescence‐activated cell sorting‐purified CD4+ T cells, CD8+ T cells, and CD4+ Treg. BM‐MSCs inhibited the production of TNF‐α, IL‐17, IL‐6, IL‐2, IFN‐γ, and IL‐9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM‐MSCs increased expression of IL‐10 and TGF‐β by CD4+ and CD8+ T cells. BM‐MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM‐MSC‐derived immunomodulation affected either naive, effector, and memory T cells.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Pedrosa

Gomes

Laranjeira

et al. 2019

J Tissue Eng Regen Med

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“…BATF and IRF4 can bind cooperatively at the IL‐9 promoter, but this is insufficient to induce transcription of IL‐9 as STAT6‐induced genes are also required (Figure ) . Consistent with this, STAT6 can also bind the IL‐9 promoter . Interestingly, BATF was increased in Th9‐polarized CD4 + T cells from atopic infants compared to healthy control infants, and T cells from Batf‐deficient mice had a reduced capacity to induce disease in a model of allergic inflammation …”

Section: Requirements For Th9 Cell Differentiationmentioning

confidence: 62%

What can primary immunodeficiencies teach us about Th9 cell differentiation and function?

2018

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Interleukin-9 (IL-9) producing CD4 + Th9 cells are a unique subset of effector cells involved in both health and disease. Th9 cells have been associated with protective immunity during parasitic infections with helminths, protozoans and extracellular pathogens, but implicated in disease states such as allergic asthma, atopic dermatitis, food allergy and autoimmune conditions including multiple sclerosis and ulcerative colitis. Here, we review the cytokine signaling pathways and downstream transcription factors required for IL-9 expression and how human primary immunodeficiencies caused by monogenic mutations can help elucidate the complex requirements for human Th9 cell differentiation. Primary immunodeficiencies are a platform for investigating IL-9 expression in primary human lymphocytes and by inference whether Th9 cells are implicated in the clinical phenotype characteristic of these patients.

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“…Th9, a de ned subset of T helper cells, has been identi ed by the potent production of IL-9 [16], which is a protein of 144 amino acids with a secretory signal sequence of 18 amino acids. Interestingly, IL-9 binds to IL-9R on target cells [17].…”

Section: Discussionmentioning

confidence: 99%

Effect of Crosstalk Between Th17 and Th9 Cells on the Activation of Dermal Vascular Smooth Muscle Cells in Systemic Sclerosis and Regulation of Tanshinone IIA

liu

2020

Preprint

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Background: To evaluate the effect of T helper 17 (Th17) cells and Th9 cells on the activation of dermal vascular smooth muscle cells (DVSMCs) in systemic sclerosis (SSc) and regulation of tanshinone IIA. Methods: The expression of interleukin 17 receptor (IL-17R) and interleukin 9 receptor (IL-9R) in the skin of SSc patients was assessed by immunofluorescence. The expression of IL-9 and IL-9R mRNA in peripheral blood mononuclear cells (PBMCs) of SSc patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proportion of Th9 cells in PBMCs of SSc patients was sorted by flow cytometry. The effect of IL-9 on the differentiation of Th17 and IL-17 on that of Th9 was detected by flow cytometry. The proportion of Th9 and Th17 cells in SSc patients was detected by flow cytometry. The level of collagen I, III, α-SMA, IL-9R, IL-17R, JNK, P38, and ERK were analyzed using Western blot (WB).Results: Th9 cells were highly expressed in SSc. IL-9 stimulated the differentiation of immature T cells into Th17 cells. IL-17 induced the differentiation of immature T cells into Th9 cells. Tanshinone IIA inhibited the differentiation of immature T lymphocytes into Th17 and Th9. WB showed that the combined action of IL-17 and IL-9 upregulated the inflammation and proliferation of DVSMCs. Anti-IL17, anti-IL9, and tanshinone IIA inhibited the functional activation of DVSMCs.Conclusions: The current results suggested that Th17 and Th9 cells induced the activation of DVSMCs in SSc through crosstalk in vitro, and tanshinone IIA inhibited the process.

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IL-9 and Th9 cells in health and diseases—From tolerance to immunopathology

Cited by 77 publications

References 78 publications

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

What can primary immunodeficiencies teach us about Th9 cell differentiation and function?

Effect of Crosstalk Between Th17 and Th9 Cells on the Activation of Dermal Vascular Smooth Muscle Cells in Systemic Sclerosis and Regulation of Tanshinone IIA

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