Basophil-associated OX40 ligand participates in the initiation of Th2 responses during airway inflammation.

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.

• Authors: Caixia Di, Xiaoliang Lin, Yanjie Zhang, Wenwei Zhong, Yufan Yuan, Tong Zhou, Junling Liu, Zhenwei Xia
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 20 Pg. 12523-36 (May 15 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 25839234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Membrane Glycoproteins
• OX40 Ligand
• Tnfsf4 protein, mouse
• Tumor Necrosis Factors

Topics

• Animals
• Asthma (genetics, immunology, pathology, therapy)
• Basophils (immunology, pathology)
• Disease Models, Animal
• Gene Expression Regulation (immunology)
• Membrane Glycoproteins (genetics, immunology)
• Mice
• Mice, Knockout
• OX40 Ligand
• Th2 Cells (immunology, pathology)
• Tumor Necrosis Factors (genetics, immunology)