Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation

Caixia Di,Xiaoliang Lin,Yanjie Zhang,Wenwei Zhong,Yufan Yuan,Tong Zhou,Junling Liu,Zhenwei Xia

doi:10.1074/jbc.m115.642637

Abstract

Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophils-primed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40(-/-) mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation.

Highlights

Basophils play a great role in the induction of Th2 cell responses in different disease contexts
Using an ovalbumin (OVA)-induced allergic airway inflammation mouse model, we previously showed that basophils acted as a primary inducer of the Th2 immunity, evident by increased OVA-specific immunoglobulin E (OVA-sIgE) and IL-4 levels both in serum and bronchial alveolar lavage fluid (BALF), and increased proportion of Th2 cells in the spleen after transfusion of lung basophils derived from OVA-challenged mice into wild-type (WT) mice [12]
The Number of Basophils in mediastinal lymph nodes (MLN) and OX40 ligand (OX40L) Expression on These Cells in the Early Phase of OVA-Immunized Mice—To confirm the role of basophils in the early phase of allergic airway inflammation, we examined the recruitment of basophils in MLN in OVA-immunized mice

Summary

Introduction

Basophils play a great role in the induction of Th2 cell responses in different disease contexts. Results: Basophils highly expressed OX40 ligand (OX40L) after activation. Adoptive transfer of activated basophils triggered a robust Th2 response and airway inflammation. Conclusion: Basophils primed Th2 responses via OX40-OX40L interaction in asthma. We found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. The adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40؊/؊ mice and mice receiving OX40L-blocked basophils. Our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation

Objectives

Results

Conclusion