Heme oxygenase‐1 directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation

• DOI: 10.1111/all.13216
• Publication Date: 2017-06-05T05:42:45Z
• Authors: X. L. Lin; J. J. Lv; J. Lv; C. X. Di; Y. J. Zhang; T. Zhou; J. L. Liu; Z. W. Xia
• Keywords: Chromatin immunoprecipitation; Immunoprecipitation

Abstract Background Specific JAK / STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO ‐1, stress‐inducible protein, inhibits Th17 cell and alleviates neutrophilic airway inflammation, but responsible molecular basis remains unclear. Methods We employed Th17‐skewing NEA mouse models to study ‐1 regulating IL ‐6‐ 3‐ ROR γt/ SOCS 3 signaling pathway control cell‐mediated inflammation. The levels cytokines expressions relative molecules were measured by ELISA , western blot, qPCR respectively. Frequency CD 4 + ‐17A ‐6R ‐23R cells was analyzed FCM . interaction between pathway‐related proteins determined co‐immunoprecipitation blot. Results Here, show hemin‐induced overexpression is required mediate this process. Specifically, decreased phosphorylation not ‐6R/ expression or 1/ 2 activation T cells. effect accompanied co‐inhibition 3, negative feedback factor activation. bound three domains on ( DNA ‐binding, linker, transactivation domains) directly regulate Conversely, either forced constitutively active mutant application small‐interfering RNA (si ) for reversed these effects. Conclusions Our data suggest exerts its inhibitory associating blocking phosphorylation. speculate hemin may be potential therapeutic candidate treatment other types immune pulmonary inflammatory‐related diseases.