| B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3 |
| 論文作者 |
Qian, GJ; Jiang, WX; Sun, DL; Sun, Z; Chen, AN; Fang, HW; Wang, JY; Liu, YZ; Yin, ZA; Wei, HM; Fang, H; Zhang, XR |
| 期刊/會議名稱 |
CELLULAR & MOLECULAR IMMUNOLOGY |
| 論文年度 |
2023 |
| 論文類別 |
Article; Early Access |
| 摘要 |
Aeroallergen sensitization, mainly mediated by lung epithelium and dendritic cells (DCs), is integral to allergic asthma pathogenesis and progression. IL-10 has a dual role in immune responses, as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation. Here, we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma. Specifically, Bcl-3-/- mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites (HDMs). IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells. Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development. IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3-Blimp-1-Bcl-6 regulation. Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization, thereby demonstrating resistance to HDM-induced asthma. Moreover, responses to HDM stimulation in Bcl-3-/- mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3+/+ mice. The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production. Thus, targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.IL-10 is released rapidly from lung plasma cells under Bcl-3-Blimp-1-Bcl-6 regulation upon house dust mite exposure and amplifies lung epithelial cell (EC)-derived CCL-20 production and subsequent dendritic cell (DC) recruitment to promote allergic sensitization in asthma. |
| 影響因子 |
24.1 |
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