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RESEARCH PRODUCT

Nitric oxide enhances Th9 cell differentiation and airway inflammation

Edwin YipTobias BoppAnne-gaelle BesnardEdgar SchmittRobert J. SalmondRodrigo GuabirabaDaniele C. NascimentoBernhard RyffelFabiane SônegoFoo Y. LiewSandra Y. FukadaHyun-dong ChangPaula B. DonateWanda Niedbala

subject

CD4-Positive T-LymphocytesInterleukin 2[SDV]Life Sciences [q-bio]Cellular differentiationNitric Oxide Synthase Type IIGeneral Physics and AstronomyMice TransgenicInflammationCell SeparationNitric OxideArticleGeneral Biochemistry Genetics and Molecular BiologyNitric oxideMicechemistry.chemical_compoundEosinophiliaSTAT5 Transcription FactormedicineAnimalsHumansInterleukin 9Cells CulturedInflammationMice Inbred BALB CMultidisciplinarybiologyNitrosylationInterleukin-9Cell DifferentiationGeneral Chemistryrespiratory systemFlow Cytometry3. Good healthCell biologyMice Inbred C57BLchemistryInterferon Regulatory FactorsImmunologyLeukocytes Mononuclearbiology.proteinInterleukin-2Mdm2Tumor Suppressor Protein p53medicine.symptomAntibodymedicine.drug

description

International audience; Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumour suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2(-/-) mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared with wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells.

yearjournalcountryeditionlanguage
2014-08-01Nature Communications
https://doi.org/10.1038/ncomms5575