Chimeric Antigen-LgDNA Nanoparticles Attenuate Airway Th2 Polarization

Ruien Chen,1,* Huamei Zou,1,* Xiuwen Ye,1,* Bailing Xie,2 Aizhi Zhang,3 Lihua Mo,4 Yu Liu,4 Huanping Zhang,5 Gui Yang,1 Pingchang Yang2 1Department of Otolaryngology, Longgang Central Hospital affiliated to Guangzhou University of Chinese Traditional Medicine Shenzhen Clinical College, Shenzhen, 518116, People’s Republic of China; 2State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University and Institute of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, 518055, People’s Republic of China; 3Department of Critical Care Medicine, Second Hospital, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of General Medicine Practice, Third Affiliated Hospital, Shenzhen University, Shenzhen, 518005, People’s Republic of China; 5Department of Allergy Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pingchang Yang; Gui Yang, Email pcy2356@163.com; guiyang1981@hotmail.comIntroduction: The therapeutic efficacy for airway allergies needs to be improved. Th2 polarization is a primary pathological feature of airway allergies. We constructed chimeric antigen-LgDNA (Lactobacillus rhamnosus DNA) nanoparticles (CAP-NPs). The effects of CAP-NPs on reconciling airway Th2 polarization were tested.Methods: In this study, disulfide bond-linked antigen-major histocompatibility complex II (MHC II)-LgDNA nanoparticles (NPs) were constructed and designated CAP-NPs. An airway Th2 polarization mouse model was established to test the effects of CAP-NPs on suppressing the Th2 response.Results: The CAP-NP components of ovalbumin (OVA), major histocompatibility complex II (MHC II), and LgDNA were confirmed in a series of laboratory tests. The CAP-NPs remained stable at pH7.2 for at least 96 h. In in vitro experiments, CAP-NPs bound to the surface of OVA-specific CD4+ T cells, which resulted in apoptosis of the antigen-specific CD4+ T cells. Removal of any of the three components from the NPs abolished the induction of apoptosis of antigen specific CD4+ T cells. CAP-NPs increased the expression of lysine-specific demethylase 5A (KDM5A) in CD4+ T cells. Histone H3K9 and the gene promoter of caspase 8 were demethylated by KDM5A, which led to transcription and expression of the caspase 8 gene. Administration of CAP-NPs significantly alleviated experimental airway Th2 polarization through activating the caspase 8-apoptosis signaling pathway.Discussion: In this paper, we constructed CAP-NPs that could induce antigen-specific CD4+ T cell apoptosis. Administration of CAP-NPs efficiently alleviated experimental airway Th2 polarization.Keywords: airway allergy, T cell, therapy, vaccine, nanoparticle