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. Author manuscript; available in PMC: 2015 Feb 7.
Published in final edited form as: Nat Commun. 2014 Aug 7;5:4575. doi: 10.1038/ncomms5575

Figure 8.

Figure 8

Schematic representation of the mechanism of NO-mediated enhancement of Th9 polarization. NO nitrosylates cysteine of MDM2 leading to the release of p53 from the MDM2-p53 complex. p53 induces IL-2 synthesis, which binds to CD25 (IL-2R α-chain) leading to STAT5 phosphorylation that activates IRF4 which binds to the promoter of Il9 for enhanced IL-9 transcription. NO also promotes IL-4Rα expression thus stimulates STAT6 phosphorylation that can also induce IRF4 expression. NO can also enhance TGFβR2 expression leading to the activation of PU.1 that can promote IL-9 transcription by binding to Il9 promoter. NO-mediated Th9 promotion is dependent on conventional TCR and CD28 activation.