BCG调控乳鼠MDSC的机制及在坏死性小肠炎中的病理意义

坏死性小肠炎(NEC)是新生儿常见的急性危重症，其发生是因免疫系统发育缺陷，导致新生儿对菌群定植等刺激产生过度炎症反应。申请者博士期间的课题组发现：髓源抑制性细胞(MDSC)通过抑制炎症，缓解乳鼠NEC症状(Nat Med.2018)。卡介苗(BCG)是新生儿出生后24小时内常规接种的一类疫苗，而早产儿不建议出生后按期接种BCG。接种BCG对早产儿免疫系统发育的影响，及与NEC易感性之间的关系，目前尚未有相关报道。申请者发现：接种BCG可显著削弱乳鼠MDSC的免疫抑制功能，导致其对NEC的易感性显著增加；过继转输MDSC则可缓解BCG所致的NEC加重。由此提出“BCG通过抑制乳鼠MDSC的功能，促进NEC发生”的假说。本项目拟探讨BCG接种对新生期MDSC细胞发育及功能的调控作用及机制，确定其在NEC疾病中的病理意义，为其临床适应症提供科学依据。

Necrotizing enterocolitis(NEC) is a common acute critical disease in neonates, which occurs because of defective immune system development, resulting in excessive inflammatory response to bacterial colonization and other stimuli in neonates. The research team during the applicant's doctoral study found that myeloid derived suppressor cells (MDSC) alleviated NEC symptoms in suckling mice by inhibiting inflammation (Nat Med. 2018). Bacille Calmette-Guerin（BCG）is a type of vaccine that is routinely given to newborns within 24 hours of birth, while BCG vaccination is not recommended for premature infants. The effect of BCG inoculation on the development of the immune system in preterm infants and its relationship with the susceptibility to NEC have not been reported. The authors found that BCG inoculation could significantly weaken the immunosuppressive function of MDSC in suckling mice, leading to a significant increase in their susceptibility to NEC. Adoptive transfer of MDSC can alleviate the aggravation of NEC caused by BCG. Thus, the hypothesis that BCG promotes NEC by inhibiting the function of MDSC in suckling mice was proposed. This project aims to explore the regulatory effect and mechanism of BCG inoculation on the development and function of neonatal MDSC cells, and to determine its pathological significance in NEC disease, and provide a scientific basis for its clinical indications.