It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the...It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin （TCS） could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4- deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-typc adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.展开更多
基金Acknowledgments We thank ProfYongjun Liu, Dangsheng Li and Yangxin Fu for helpful comments and Dr Sheri Skinner for reviewing the manuscript and for constructive suggestions. This work was supported by grants from the National Natural Science Foundation of China （30530700, 30623003, 30600568, 30721065, 90713044, 30600308, 30801011, 30870126） and CAS project （KSCX1-YW-R-43）, grant from SIBS project （2007KIP301）, grants from the Ministry of Science and Technology （2006CB504300, 2007CB512404, 2006AA02A247, 20072714）, the Technology Commission of Shanghai Municipality （88014199, 07DZ22916, 07XD14033, 064319034, 08431903004, 2008ZX10206, 08DZ2291703）, EU project （FP6-2005-SSP-5-B, SP5B-CT-2006-044161） and from the E-institutes of Shanghai Universities Immunology Division.
文摘It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin （TCS） could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4- deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-typc adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.
