Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic airway inflammation. Issue 11 (12th October 2018)

• Record Type: Journal Article
• Authors: Lv, Jiajia; Yu, Qianying; Lv, Jie; Di, Caixia; Lin, Xiaoliang; Su, Wen; Wu, Min; Xia, Zhenwei
• Is Part Of: European journal of immunology. Volume 48:Issue 11(2018)
• Page Start: 1838
• Page End: 1850
• Publication Date: 2018-10-12
• Subjects: TSLP -- TLR2 -- signaling pathways -- basophils -- type 2 immune responses; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847663
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Epithelial cells (ECs)‐derived cytokines are induced by different stimuli through pattern recognition receptors (PRRs) to mount a type‐2‐cell‐mediated immune response; however, the underlying mechanisms are poorly characterized. Here, we demonstrated asthmatic features in both primary bronchial epithelial cells (pBECs) and mouse model using several allergens including ovalbumin (OVA), house dust mite (HDM), or Alternaria alternata . We found that toll‐like receptor 2 (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various allergens, leading to recruitment of circulating basophils into the lung via C‐C chemokine ligand‐2 (CCL2). TLR2 expression increased thymic stromal lymphopoietin (TSLP) production through the NF‐κB and JNK signaling pathways to extend the survival of recruited basophils and resident DCs in the lung, predisposing a type‐2‐cell‐mediated airway inflammation. Conversely, TLR2 deficiency impairedsecretion of TSLP and CCL2, decreased infiltration of lung basophils, and increased resistance to Th2 response. Blocking TSLP also phenocopied these phenomena. Our findings reveal a pro‐inflammatory role of airway ECs through a TLR2‐dependent TSLP production, which may have implication for treating allergic asthma. Abstract : Allergen‐induced TLR2 on airway epithelia promotes production of TSLP and CCL2 through NF‐KB and JNK signaling resulting in recruitment of basophils and initiates Th2 responses. The TLR2 expression is correlated with eosinophilic airway inflammation in asthmatic mice models and suggests that TLR2 may be a therapeutic target for allergic asthma.