BLT1 signaling in epithelial cells mediates allergic sensitization via promotion of IL-33 production
| Autor: | Huabin Li, Rui He, Lixia Du, Zhengrong Chen, Qibin Leng, Yingluo Xiong, Xinyi Cui, Wenli Mi, Jiaoyan Lv, Wenjing Li, Hong Zhou |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Leukotriene B4 Immunology Receptors Leukotriene B4 Inflammation Lymphocyte Activation Allergic sensitization 03 medical and health sciences chemistry.chemical_compound Mice T-Lymphocyte Subsets Papain medicine Hypersensitivity Immunology and Allergy Animals Lymphocytes Protein kinase B Sensitization Innate lymphoid cell Epithelial Cells respiratory system Allergens Interleukin-33 Interleukin 33 030104 developmental biology medicine.anatomical_structure chemistry Cytokines Immunization Signal transduction medicine.symptom Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Allergy. 74(3) |
| ISSN: | 1398-9995 |
| Popis: | Background Epithelial cells (ECs) play a crucial role in allergic sensitization to inhaled protease allergens by instructing type 2 innate lymphoid cells (ILC2) and dendritic cells (DCs) via release of pro-type 2 cytokines, particularly interleukin-33 (IL-33). Leukotriene B4 (LTB4) is a well-known leukocyte chemoattractant via engagement of its receptor 1 (BLT1). However, the role of LTB4-BLT1 axis in allergic sensitization via activation of ECs is still unknown. Methods We evaluated the effect of LTB4-BLT1 axis on IL-33 expression and ILC2 activation in vivo and in vitro. Chimeric mice were established to evaluate the contribution of BLT1 expression in nonimmune cell to allergic sensitization. Results Genetical or pharmacological interruption of LTB4-BLT1 axis during sensitization phase markedly reduced papain-induced IL-33 expression, decreased ILC2 activation and DC migration, thereby impairing the priming of allergic Th2 responses. Furthermore, papain inhalation induced a rapid release of LTB4 preceding IL-33, and intranasal administration of LTB4 to naive WT mice significantly increased IL-33 expression and ILC2 activation in lung, which was absent in Il33-/- or Ltb4r1-/- mice. Furthermore, BLT1 was expressed in primary mouse ECs or normal human bronchial ECs (NHBE), and papain induced LTB4 release by NHBE, which in turn amplified IL-33 production dependent on Akt activation via BLT1. Consequently, bone marrow chimeric mice lacking BLT1 in radio-resistant structural cells failed to develop allergic lung inflammation to papain. Conclusion Our study reveals a functional role of LTB4-BLT1 axis in nonimmune cells, most likely lung ECs, in controlling allergic sensitization as an upstream regulator of IL-33. |
| Databáze: | OpenAIRE |
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