Collaborative interactions between type 2 innate lymphoid cells and antigen-specific CD4+ Th2 cells exacerbate murine allergic airway diseases with prominent eosinophilia.
Collaborative interactions between type 2 innate lymphoid cells and antigen-specific CD4+ Th2 cells exacerbate murine allergic airway diseases with prominent eosinophilia.
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DOI：
10.4049/jimmunol.1400951
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发表时间：
2015-04-15
期刊：
影响因子：
--
通讯作者：
Wang YH
中科院分区：
文献类型：
--
作者：
Liu B;Lee JB;Chen CY;Hershey GK;Wang YH
2型先天淋巴样细胞（ILC2s2）和获得性分化簇4 (CD43)+Th2和Th17细胞参与实验性哮喘的发病机制；然而，它们在年龄驱动的慢性小鼠过敏性气道疾病恶化中的作用仍然难以捉摸。在本研究中，我们报告了在休息的小鼠中，仅用OVA Ag重复鼻内再次刺激足以引发气道高反应性，突出的嗜酸性粒细胞炎症，并显着增加血清OVA特异性IgG1和IgE，这些小鼠先前发生了小鼠过敏性气道疾病。重复接种OVA的召回反应优先触发肺部OVA特异性CD4+Th2细胞的进一步增加，而CD4+Th17和ILC2细胞数量保持不变。此外，Stat6−/−/IL-17-GFP小鼠的获得性CD4+Th17细胞，或CD4+T细胞切除小鼠的先天ILC2s细胞，未能对OVA Ag产生过敏回忆反应。在反复的卵母细胞再激发或CD4+T细胞消融后，CD4+Th2细胞的增加或减少分别导致IL-25和IL-33刺激下肺ILC2s产生IL-13的增加或减少。反过来，ILC2s增强了ag介导的共培养CD4+Th2细胞的增殖及其细胞因子的产生，并促进了过继转移ag特异性CD4+Th2细胞驱动的嗜酸性气道炎症和杯状细胞增生。因此，这些结果表明，对反复出现的Ag暴露的过敏回忆反应优先触发Ag特异性CD4+Th2细胞的增加，这促进了获得性CD4+Th2细胞和先天ILC2s之间的协同相互作用，从而驱动具有嗜酸性表型的小鼠过敏性气道疾病的恶化。
Type-2 innate lymphoid cells (ILC2s2) and the acquired cluster of differentiation 4 (CD43)+Th2 and Th17 cells contribute to the pathogenesis of experimental asthma; however, their roles in Ag-driven exacerbation of chronic murine allergic airway diseases remain elusive. Herein, we report that repeated intranasal re-challenges with only OVA Ag were sufficient to trigger airway hyperresponsiveness, prominent eosinophilic inflammation, and significantly increased serum OVA-specific IgG1 and IgE in rested mice that previously developed murine allergic airway diseases. The recall response to repeated OVA inoculation preferentially triggered a further increase of lung OVA-specific CD4+Th2 cells, whereas CD4+Th17 and ILC2 cell numbers remained constant. Furthermore, the acquired CD4+Th17 cells in Stat6−/−/IL-17-GFP mice, or innate ILC2s in CD4+T cell-ablated mice, failed to mount an allergic recall response to OVA Ag. After repeated OVA re-challenge or CD4+T cell ablation, the increase or loss of CD4+Th2 cells resulted in an enhanced or reduced IL-13 production by lung ILC2s in response to IL-25 and IL-33 stimulation, respectively. In return, ILC2s enhanced Ag-mediated proliferation of co-cultured CD4+Th2 cells and their cytokine production, and promoted eosinophilic airway inflammation and goblet cell hyperplasia driven by adoptively transferred Ag-specific CD4+Th2 cells. Thus, these results suggest that an allergic recall response to recurring Ag exposures preferentially triggers an increase of Ag-specific CD4+Th2 cells, which facilitates the collaborative interactions between acquired CD4+Th2 cells and innate ILC2s to drive the exacerbation of a murine allergic airway diseases with an eosinophilic phenotype.
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