Kelly-Welch Ann E, Melo Marco E F, Smith Elizabeth, Ford Andrew Q, Haudenschild Christian, Noben-Trauth Nancy, Keegan Achsah D
Departments of Immunology, Holland Laboratory, American Red Cross, Rockville, MD 20855, USA.
J Immunol. 2004 Apr 1;172(7):4545-55. doi: 10.4049/jimmunol.172.7.4545.
Recent studies have suggested the IL-4Ralpha expressed on lung epithelium is necessary for TH2-mediated goblet cell differentiation and mucus hypersecretion in a murine model of allergic lung disease. However, the IL-4Ralpha is expressed on numerous cell types that could contribute to the overall pathology and severity of asthma. The relative role of the receptor on these cells has not yet been conclusively delineated. To dissect the contribution of IL-4Ralpha in the development of pulmonary allergic responses, we generated murine radiation bone marrow (BM) chimeras. BM from IL-4Ralpha(+) or IL-4Ralpha(-) mice was transferred into recipient mice that expressed or lacked IL-4Ralpha. In the absence of IL-4Ralpha in recipient mice, there was no goblet cell metaplasia or mucus hypersecretion in response to OVA, even in the presence of TH2 cells and substantial eosinophilic infiltration. More importantly, we found that expression of the IL-4Ralpha on a nonlymphoid, MHC class II(+), BM-derived cell type contributes to the severity of inflammation and mucus production. These results suggest that IL-4 and IL-13 contribute to the development of allergic inflammation by stimulating a complex interaction between IL-4Ralpha(+) cell types of both bone marrow and non-bone marrow origin.
近期研究表明，在变应性肺疾病小鼠模型中，肺上皮细胞表达的白细胞介素-4受体α（IL-4Rα）对于TH2介导的杯状细胞分化和黏液高分泌是必需的。然而，IL-4Rα在多种细胞类型上表达，这些细胞类型可能会导致哮喘的整体病理和严重程度。该受体在这些细胞上的相对作用尚未得到明确界定。为了剖析IL-4Rα在肺部变应性反应发展中的作用，我们构建了小鼠辐射骨髓（BM）嵌合体。将来自IL-4Rα(+)或IL-4Rα(-)小鼠的骨髓移植到表达或缺乏IL-4Rα的受体小鼠中。在受体小鼠缺乏IL-4Rα的情况下，即使存在TH2细胞和大量嗜酸性粒细胞浸润，对卵清蛋白（OVA）也没有杯状细胞化生或黏液高分泌。更重要的是，我们发现IL-4Rα在一种非淋巴细胞、MHC II类(+)、骨髓来源的细胞类型上的表达会导致炎症严重程度和黏液产生。这些结果表明，白细胞介素-4（IL-4）和白细胞介素-13通过刺激骨髓来源和非骨髓来源的IL-4Rα(+)细胞类型之间的复杂相互作用，促进变应性炎症的发展。
