摘要
Neutrophils are involved in the pathogenesis of allergy.However,the contribution of the different functionally polarized neutrophils in allergy needs to be clarified.We sought to define the characteristics of interleukin(IL)-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis.Freshly isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by realtime PCR.The gene expression profile of IL-33-induced neutrophils was determined by microarray assay.Adoptive transfer assay was used to investigate the function of IL-33-induced neutrophils in an ovalbumin(OVA)-induced allergic asthma model.IL-33-treated neutrophils selectively produced IL-4,IL-5,IL-9 and IL-13(referred as to N(IL-33)cells)and displayed a distinctive gene expression profile in sharp contrast to resting and lipopolysaccharide(LPS)-treated neutrophils.IL-33-induced neutrophils expressed high Levels of IL-1R2 on cell surface,whereas resting and LPS-treated neutrophils did not,indicating IL-1R2 might be used as a biomarker for N(IL-33)cells.Importantly,N(IL-33)neutrophils exist in the lungs of OVA-induced allergic asthma mice.Adoptive transfer of N(IL-33)neutrophils significantly promotes the severity of the lung pathogenesis in this model.IL-33 induces neutrophil polarization through c-Jun N-terminal kinase-and nuclear factor-κB-dependent pathways.A previously unappreciated neutrophil polarization driven by IL-33 with unique cell surface markers and cytokine/chemokineproducing gene profile was defined.The newly identified N(IL-33)subpopulation may have significant contribution to IL-33-related pathogenesis.
基金
supported by grants from the National Natural Science Foundation of China for General and Key Programs(81530049 and 81130055 to YZ)
Knowledge Innovation Program of Chinese Academy of Sciences(XDA04020202-19 to YZ)
the CAS/SAFEA International Partnership Program for Creative Research Teams(to YZ)
Beijing Municipal Hospital Authority‘Yangfan Program’(ZYLX201408 to XZ).
