Chemerin/ChemR23通过诱导未成熟的树突状细胞参与呼吸道合胞病毒感染的免疫调节

Participation of Chemerin/ChemR23 in Immune Regulation of Respiratory Syncytial Virus Infection Through Induction of Immature Dendritic Cells

目的:探讨Chemerin/ChemR23通过作用于树突状细胞(DCs)对呼吸道合胞病毒(RSV)肺炎免疫应答的调节作用。方法:纳入普通RSV肺炎患儿46例,对照组外科无肺部症状的手术患儿19例。获取外周血分离培养树突状细胞,两组患儿均使用磷酸盐缓冲液(PBS)和Chemerin刺激树突状细胞至48 h,分别检测树突状细胞ChemR23、CD80和CD86的表达。结果:(1)外周血分离出的树突状细胞,培养第7天,表面出现毛刺样凸起及典型的树突状细胞形态改变。培养第15天,细胞表面毛刺明显增多并呈聚集样改变。培养第7天的悬浮细胞ChemR23、CD80、CD86均表达阳性。(2)RSV肺炎患儿外周血DCs经Chemerin刺激24 h和48 h后ChemR23阳性表达显著高于PBS组(29.3%±6.5%vs 24.8%±5.8%,25.2%±8.3%vs 21.0%±8.3%,P均<0.01);对照组中,DCs经Chemerin刺激24 h和48 h后ChemR23阳性表达率与PBS组比较差异均无统计学意义。(3)RSV肺炎组中,DCs经Chemerin刺激24 h和48 h后CD80阳性表达率显著低于PBS组(28.1%±6.0%vs 33.4%±7.4%,24.0%±8.7%vs 30.8%±9.8%,P均<0.01)。对照组中,DCs经Chemerin刺激24 h后CD80阳性表达率与PBS组比较差异无统计学意义。但DCs经Chemerin刺激48 h后,CD80阳性率(29.2%±7.4%)显著低于PBS组(35.4%±7.6%,P<0.01)。(4)RSV肺炎组中,DCs经Chemerin刺激24 h和48 h后CD86阳性率显著低于PBS组(32.9%±6.4%vs 36.4%±7.7%,26.6%±10.9%vs 30.6%±10.8%,P均<0.01)。DCs经Chemerin刺激24 h后CD86阳性表达率与PBS组比较差异无统计学意义。但DCs经Chemerin刺激48 h后,CD86阳性率(34.1%±8.2%)则显著低于PBS组(40.9%±8.8%,P<0.01)。结论:早期普通RSV肺炎中,Chemerin/ChemR23可能通过下调共刺激分子CD80和CD86的表达,特异诱导树突状细胞不成熟,从而与抗炎和后续哮喘发生相关。

Objective:To probe into the regulation of Chemerin/ChemR23 on immune response to respiratory syncytial virus(RSV)pneumonia through its action on dendritic cells(DCs).Methods:A total of 46 children with common RSV pneumonia and 19 children without pulmonary symptoms in surgery in the control group were enrolled.Peripheral blood was obtained for isolation and culture of dendritic cells.Both groups were stimulated with phosphate buffer solution(PBS)and Chemerin for 48 h,and the expressions of ChemR23,CD80 and CD86 in dendritic cells were respectively detected.Results:(1)Dendritic cells isolated from peripheral blood showed burr-like protrusions and typical morphological changes on the surface on the 7^(th) d of culture.On the 15^(th) d of culture,the burrs on the cell surface increased significantly and showed aggregated changes.ChemR23,CD80 and CD86 were all positive in suspension cells on the 7^(th) d of culture.(2)The positive expression of ChemR23 in DCs of children with RSV pneumonia after Chemerin stimulation for 24 h and 48 h was significantly higher than that in PBS group(29.3%±6.5%vs 24.8%±5.8%,25.2%±8.3%vs 21.0%±8.3%,P<0.01).In the control group,the difference of ChemR23 positive expression rate in DCs after Chemerin stimulation for 24 h and 48 h was not statistically significant compared with the PBS group.(3)In the RSV pneumonia group,the positive expression rate of CD80 after Chemerin stimulation for 24 h and 48 h was significantly lower than that of the PBS group(28.1%±6.0%vs 33.4%±7.4%,24.0%±8.7%vs 30.8%±9.8%,P<0.01).In the control group,the positive expression rate of CD80 after Chemerin stimulation for 24 h was not significantly different from the PBS group.Yet after DCs were stimulated by Chemerin for 48 h,the positive rate of CD80(29.2%±7.4%)was significantly lower than that of the PBS group(35.4%±7.6%,P<0.01).(4)In the RSV pneumonia group,the positive rate of CD86 in DCs after Chemerin stimulation for 24 h and 48 h was significantly lower than that of the PBS group(32.9%±6.4%vs 36.4%±7.7%,26.6%±10.9%vs 30.6%±10.8%,P<0.01).There was no significant difference in the positive expression rate of CD86 between DCs stimulated by Chemerin after 24 h and PBS group.However,the positive expression rate of CD80(34.1%±8.2%)in DCs after Chemerin stimulation for 48 h was significantly lower than that of PBS group(40.9%±8.8%,P<0.01).Conclusion:In early common RSV pneumonia,Chemerin/ChemR23 may specifically induce immature DCs by down-regulating the expression of costimulatory molecules CD80 and CD86,which may be associated with anti-inflammatory and subsequent asthma.