IL-33-matured dendritic cells promote Th17 cell responses via IL-1β and IL-6

Park, Su Ho; Kim, Myun Soo; Lim, Hui Xuan; Cho, Daeho; Kim, Tae Sung

doi:10.1016/j.cyto.2017.07.022

Cited by 41 publications

(32 citation statements)

References 39 publications

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“…As shown by other investigators, BMDCs express IL-33R (4,(25)(26)(27)(28). Consequently, stimulation of wt, but not of t1/st2 2/2 (il-33r 2/2 ), BMDCs with IL-33 induced the production of IL-6 and IL-13 (Supplemental Fig.…”

Section: Il-33 Stimulation Does Not Induce Ikba Degradation In Bmdcssupporting

confidence: 62%

The p38-MK2/3 Module Is Critical for IL-33–Induced Signaling and Cytokine Production in Dendritic Cells

Göpfert

Andreas

Weber

et al. 2018

The Journal of Immunology

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IL-33 is an IL-1 cytokine superfamily member. Binding of IL-33 to the IL-33R induces activation of the canonical NF-κB signaling and activation of MAPKs. In bone marrow-derived dendritic cells, IL-33 induces the production of IL-6, IL-13, and TNF-α. However, the signaling pathways resulting in IL-33-induced effector functions of dendritic cells are unknown. In this article, we show that the IL-33-induced cytokine production is only partly dependent on p65. Thereby, p65 mediates the production of IL-6, but not of IL-13, whereas the p38-Mapk-activated protein kinases 2/3 (MK2/3) signaling module mediates the IL-13, but not the IL-6, production. In addition, GM-CSF, which is critical for the differentiation and proliferation of bone marrow-derived dendritic cells, potentiates the p65-dependent IL-6 and the p38-MK2/3-dependent IL-13 production. Furthermore, we found that effective TNF-α production is only induced in the presence of GM-CSF and IL-33 via the p38-MK2/3 signaling module. Taken together, we found that the p38-MK2/3 signaling module is essential to mediate IL-33-induced cytokine production in dendritic cells.

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Section: Il-33 Stimulation Does Not Induce Ikba Degradation In Bmdcssupporting

confidence: 62%

The p38-MK2/3 Module Is Critical for IL-33–Induced Signaling and Cytokine Production in Dendritic Cells

Göpfert

Andreas

Weber

et al. 2018

The Journal of Immunology

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“…29,30 Furthermore, IL33 has been shown to induce BMDC to release IL6 in a dose dependent fashion and co-culture of IL33 stimulated BMDC with CD4 + T-cells promotes IL33-induced IL17A release. 9,20 Accordingly, IL33 stimulated BMDC promoted Th17 responses via IL1β and IL6. 20 Taken together with our findings that DEP and HDM exposures promote IL6 release and HDM + DEP -induced IL6 secretion is impaired in ST2 −/− lung cells, the results suggest that DEP + HDM co-exposure induces IL6 secretion, in part via IL33 stimulated DC, promoting a mixed Th2/Th17 response.…”

Section: Discussionmentioning

confidence: 98%

“…9,20 Accordingly, IL33 stimulated BMDC promoted Th17 responses via IL1β and IL6. 20 Taken together with our findings that DEP and HDM exposures promote IL6 release and HDM + DEP -induced IL6 secretion is impaired in ST2 −/− lung cells, the results suggest that DEP + HDM co-exposure induces IL6 secretion, in part via IL33 stimulated DC, promoting a mixed Th2/Th17 response.…”

Section: Discussionmentioning

confidence: 98%

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IL33 contributes to diesel pollution‐mediated increase in experimental asthma severity

Brandt

Bolcas

Ruff

et al. 2020

Allergy

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Background Exposure to traffic pollution, notably diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbations. The contribution of cytokines generated by stressed lung epithelial cells (IL25, IL33, TSLP) to DEP‐induced asthma severity remains poorly understood. Methods BALB/c mice were exposed intratracheally once to DEP or 9 times over 3‐weeks to either saline, DEP, and/or house dust mite extract (HDM). Airway hyper‐responsiveness (AHR), pulmonary inflammation, and T‐cell subsets were assessed 24 hours after the last exposure in mice sufficient and deficient for the IL33 receptor ST2. Results DEP exposure induces oxidative stress, IL6, neutrophils and pulmonary accumulation of IL33, but not IL25 or TSLP or other features of allergic disease. When mice are co‐exposed to DEP and low doses of HDM, DEP increases IL33 lung levels and Th2 responses. ST2 deficiency partially protected mice from HDM + DEP induced AHR in association with decreased type 2 inflammation and lung levels of IL5+IL17A+ co‐producing T‐cells. Upon in vitro HDM challenge of lung cells from HDM ± DEP exposed ST2−/− mice, secretion of IL5, IL13, IL6 and IL17A was abrogated by a mechanism involving IL33 signaling in both dendritic cells and T‐cells. HDM + DEP exposed bone marrow derived dendritic cells and IL33 pulsed BMDC promote a mixed Th2/Th17 response that was dependent on ST2 expression by CD4+ T‐cells. Conclusion IL33 contributes to DEP mediated increase in allergen‐induced Th2 inflammation and AHR in a mouse model of severe steroid resistant asthma, potentially through the accumulation of pathogenic IL5+IL17A+ CD4+ effector T‐cells.

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“…Melatonin regulates the expression of in ammatory factors in the submandibular glands of NOD/Ltj mice T cell proliferation depends on many lymphocyte-activating factors. IL-1β and IL-6 are early markers of the in ammatory response and play key roles in promoting T cell activation and proliferation [12]. We detected the expression of IL-1β and IL-6 in the submandibular glands of NOD/Ltj mice after different treatments by immunohistochemistry (cells stained with each antibody are shown in brown).…”

Section: Melatonin Alleviates Experimental Sjögren's Syndrome Featurementioning

confidence: 99%

Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome

Liu¹,

Weng²,

Yu³

et al. 2020

Preprint

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Background Excessive inflammatory reactions participate in primary Sjögren’s syndrome (pSS) progression. In addition, biological clock genes have been detected in the salivary glands, which indicates that clock genes regulate the growth and development of the salivary glands as well as the quality and quantity of saliva secretion. Melatonin is an amine hormone secreted by the pineal gland that has many physiological functions, such as regulating immunity and correcting disorder in the biological clock rhythm. The purpose of this study was to clarify the correlation between pSS and the biological clock rhythm and explore the possibility of applying melatonin to treat pSS. Methods Melatonin (10 mg/kg/d or 15 mg/kg/d) or vehicle was administered to NOD/Ltj mice by intraperitoneal injection for 4 weeks. Clock gene expression levels in labial gland biopsy specimens from pSS patients and submandibular gland specimens from mice were measured by Western blotting (WB) and RT-PCR. The salivary flow rate of mice was measured at 12, 14, and 16 weeks. The severity of lymphocyte infiltration in the salivary glands was analysed by haematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining were used to detect the expression levels of related inflammatory factors in mice. The percentages of Th17, Th2, and Treg cells were analysed by flow cytometry. Results There was a distinct expression profile for clock genes in pSS patients compared with controls. Continuous melatonin administration improved salivary gland function in NOD/Ltj mice, with decreased lymphocyte infiltration in the submandibular glands and reduced related inflammatory factor expression in the serum and salivary glands. Melatonin treatment skewed T cells towards the Treg and Th2 subsets while suppressing Th17 responses. Additionally, melatonin administration regulated clock gene expression in NOD/Ltj mice. Conclusion pSS pathogenesis and progression are correlated with abnormal circadian gene expression. Melatonin improves the hypofunction of the salivary glands and inhibits the inflammatory development of pSS in NOD/Ltj mice. This study provides a theoretical basis and potential approach for the clinical prevention and treatment of pSS.

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IL-33-matured dendritic cells promote Th17 cell responses via IL-1β and IL-6

Cited by 41 publications

References 39 publications

The p38-MK2/3 Module Is Critical for IL-33–Induced Signaling and Cytokine Production in Dendritic Cells

The p38-MK2/3 Module Is Critical for IL-33–Induced Signaling and Cytokine Production in Dendritic Cells

IL33 contributes to diesel pollution‐mediated increase in experimental asthma severity

Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome

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