Investigation of the Role of Cholera Toxin in Assisting the Initiation of the Antigen-Specific Th2 Response

Bai-Sui Fengab, Peng-Yuan Zhenga, Xiao Chenb, Xue-Qing Liaob & Ping-Chang Yangb*a Department of Gastroenterology, Zhengzhou University School of Medicine, Zhengzhou, Chinab Brain Body Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada† Correspondence: Ping-Chang Yang, BBI-T3330, 50 Charlton Ave East, St. Joseph Hospital, Hamilton, ON, Canada, L8N 4A6 yangp@mcmaster.caSkewed Th2 polarization and tissue mastocytosis are the main features of allergy; but how the antigen-specific Th2 polarization initiated remains unclear. The present study shows that cholera toxin (CT) activates mouse bone marrow mast cells (BMMC) to release interleukin (IL)-4. The activation process involved in Toll-like receptor 4, nucleotide oligomerisation domain 1, activate signal transducer and activator of transcription 6 (STAT6), and IL-4. Activated mast cell-derived IL-4 in synergy with co-existing antigen information provided by dendritic cells drives naïve CD4+ T cells to differentiate into antigen-specific Th2 cells. The finding demonstrates that concurrent exposure to microbial products, such as CT, and antigen-loaded dendritic cells plays a critical role in the initiation of antigen-specific Th2 response in the body; this notion is supported by the concurrent adoptive transfer with CT-pulsed BMMCs and antigen-loaded BMDCs that induced antigen-specific Th2 response and hypersensitivity reaction in the intestine.