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BLT 1 signaling in epithelial cells mediates allergic sensitization via promotion of IL ‐33 production
Author(s) -
Xiong Yingluo,
Cui Xinyi,
Li Wenjing,
Lv Jiaoyan,
Du Lixia,
Mi Wenli,
Li Huabin,
Chen Zhengrong,
Leng Qibin,
Zhou Hong,
He Rui
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13656
Subject(s) - sensitization , immunology , allergic inflammation , thymic stromal lymphopoietin , innate lymphoid cell , chemistry , inflammation , biology , immune system , innate immune system
Background Epithelial cells ( EC s) play a crucial role in allergic sensitization to inhaled protease allergens by instructing type 2 innate lymphoid cells ( ILC 2) and dendritic cells ( DC s) via release of pro‐type 2 cytokines, particularly interleukin‐33 ( IL ‐33). Leukotriene B4 ( LTB 4) is a well‐known leukocyte chemoattractant via engagement of its receptor 1 ( BLT 1). However, the role of LTB 4‐ BLT 1 axis in allergic sensitization via activation of EC s is still unknown. Methods We evaluated the effect of LTB 4‐ BLT 1 axis on IL ‐33 expression and ILC 2 activation in vivo and in vitro. Chimeric mice were established to evaluate the contribution of BLT 1 expression in nonimmune cell to allergic sensitization. Results Genetical or pharmacological interruption of LTB 4‐ BLT 1 axis during sensitization phase markedly reduced papain‐induced IL ‐33 expression, decreased ILC 2 activation and DC migration, thereby impairing the priming of allergic Th2 responses. Furthermore, papain inhalation induced a rapid release of LTB 4 preceding IL ‐33, and intranasal administration of LTB 4 to naïve WT mice significantly increased IL ‐33 expression and ILC 2 activation in lung, which was absent in Il33 −/− or Ltb4r1 −/− mice. Furthermore, BLT 1 was expressed in primary mouse EC s or normal human bronchial EC s ( NHBE ), and papain induced LTB 4 release by NHBE , which in turn amplified IL ‐33 production dependent on Akt activation via BLT 1. Consequently, bone marrow chimeric mice lacking BLT 1 in radio‐resistant structural cells failed to develop allergic lung inflammation to papain. Conclusion Our study reveals a functional role of LTB 4‐ BLT 1 axis in nonimmune cells, most likely lung EC s, in controlling allergic sensitization as an upstream regulator of IL ‐33.