低剂量IL-2选择性调节CD4+T细胞亚群可塑性在孤独症中的机理研究

孤独症谱系障碍（ASD）被WHO列为儿童精神疾病第一位，至今发病机制不清、无有效治疗方法，成为严重影响儿童健康的全球公共卫生问题。研究发现免疫异常与ASD发病相关，免疫干预可改善ASD症状，但机理不清。我们发现ASD患儿CD4+Th1,2,17细胞及炎性因子升高，调节性Treg细胞及TGF-β下降，IFN-γ高Treg低的患儿症状更重。BTBR T~(+)tf/J小鼠Th17高、TGF-β低。我们设想CD4+Teff与Treg间的失衡引起的免疫炎症参与了ASD病因或加重ASD。已知低剂量IL-2能选择性激活Treg、抑制Th17, Tfh细胞活化、控制炎症，治疗多种自身免疫性疾病安全有效。目前国内外尚无低剂量IL-2治疗ASD的报道。本研究拟继续扩大临床样本检测、用低剂量IL-2重塑BTBR小鼠CD4+T细胞亚群，从细胞免疫角度探索ASD的发病原因，寻找治疗ASD可能的免疫靶点及策略。

Autism spectrum disorder (ASD) is listed as the first mental disease in children by WHO. Up to now, the pathogenesis is unclear and there is no effective treatment, which has become a global public health problem that seriously affects children's health. It was found that immune abnormality was closely related to the onset of ASD and immune intervention was useful for ameliorating the symptoms of autism although the mechanism was not clear. We found that CD4+ Th1,2,17 cell subsets and inflammatory factors increased, whereas regulatory Treg cells decreased in children with ASD. The symptoms of ASD children with high concentration of IFN-γ and low percentage of Treg were more serious. We also found that the Th17 increased and Treg decreased in BTBR T~(+)tf/J autism mice. We then hypothesized that the dysregulation between CD4 + Teff and Treg cell subsets might involve in the cause or aggravation of ASD. It has been confirmed that low dose IL-2 can selectively activate Treg cells, inhibit Th17 and TFH cells, control immune inflammation, and treat a variety of autoimmune diseases safely and effectively. At present, there is no report about the treatment of ASD with low dose IL-2 at home and abroad. In this study, we intend to further expand the detection of clinical sample size, reconstruct the CD4+T cell subsets of BTBR T~(+)tf/J mice with low-dose IL-2, hope to explore the pathogenesis of ASD from the perspective of cellular immunity, and to find out the possible immune targets and strategies for the treatment of ASD.