title: Platelets promote allergic asthma through the expression of CD154.
abstract: Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe leukocyte infiltration and lung inflammation, elevated IgE production and strengthened T helper 2 (Th2) responses in asthma-induced mice. Accordingly, platelet depletion compromised allergic asthma progression. Cd154-deficient platelets failed to promote asthma development, indicating the requirement of CD154 for platelets to promote asthma progression. The mechanistic study showed that platelets inhibited the induction of Foxp3(+) regulatory T cells both in vivo and in vitro at least partially through CD154, providing an explanation for the increase of Th2 responses by platelet transfer. Our study reveals the previously unknown role of platelet CD154 in the promotion of asthma progression by polarizing Th2 responses and inhibiting regulatory T-cell generation and thus provides a potential clue for allergic disease interventions.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.|National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Respiration, General Hospital of Shenyang Military Region, Shenyang, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.|National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D001792:Blood Platelets / Q000276:immunology / Q000473:pathology*; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D007073:Immunoglobulin E / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D015539:Platelet Activation; D017713:Platelet Transfusion; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D023201:CD40 Ligand; D007073:Immunoglobulin E; D010047:Ovalbumin