2019美国胸科学会年会（ATS 2019）正在进行，上海复旦大学附属中山医院陈智鸿副教授和青岛大学附属医院的刘晓静博士两项研究入选此次壁报，医脉通就壁报研究内容对陈智鸿副教授和刘晓静博士进行了专访。

医脉通：请两位老师给我们介绍一下您这次会议带来的壁报内容

陈教授：我这次带来的一个壁报是关于树突状细胞（DC细胞）过继免疫治疗哮喘方面的作用，我们发现DC被脂多糖（Lps）激活后，将其注射至卵清蛋白（OVA）致敏的老鼠体内，可以产生免疫抑制作用，主要表现为老鼠的OVA导致的肺部病理炎症评分降低。其中涉及的一个机制主要是白细胞介素10（IL-10）和转化生长因子-β（TGF-β）介导的抑制作用，这个是我们主要的研究结果。这个结果将来的意义是，有一些重症哮喘患者可能缺乏相应的药物治疗，通过这样一种DC免疫抑制作用，可能会在细胞治疗方面开拓一个新的领域。 

刘博士：我的研究内容主要是关于白细胞介素27的通过气道局部的给药可以缓解哮喘的急性发作，主要是对哮喘有预防性作用。同时气道局部给予白细胞介素27还会在局部的微环境中形成一个正循环，进一步的缓解哮喘的急性发作。这个研究后期应用到临床，可以在人体中尝试进行雾化吸入，可能对哮喘的治疗有所帮助。

医脉通：今年的ATS您觉得有什么亮点或您关注的研究内容？

陈教授：我的研究领域主要有两个，慢性气道疾病和间质性肺病，所以来了以后我也关注这方面有哪些进展，因为我们知道慢性气道疾病和感染关系比较密切，现在非结核分枝杆菌感染的发生越来越多，诊断上相对来说也比较困难。我关注到今年ATS对非结核分枝杆菌（NTM）有很多专题，包括如何做流行病学研究，今年会议上就讲了人与人之间是否存在NTM的相互传播，另外是有没有一些新的方法来诊断NTM。比如通过支气管镜灌洗获得的标本来做病原学检测，还有就是通过一些更好的方法，比如直接通过基因测序来做NTM的深入研究，所以我觉得在后面几天还会关注NTM的一些专门讲座，这会带给我们一些新的观点和看法。 

医脉通：谢谢。 

附

陈智鸿副教授壁报摘要

Rationale: It is still controversial of the functional states of DC and SOCS3 gene deletion of DC in the pathogenesis of allergic inflammatory diseases. In this study, we observed the effect of SOCS3-/- and SOCS3+/+ bone marrow-derived DCs (BMDCs) under distinct differential condition, when adoptively transferred, on the airway inflammation in OVA-sensitized asthmatic mice and explored the underlying molecular mechanisms. 

Methods: BMDCs were pulsed with LPS for 24h to promote its maturation which named as DClps (for the unpulsed BMDCs, named as DCim). DClps and Dcim, SOCS3-/- and SOCS3+/+ BMDCs under LPS pulsed were adoptively transfered into OVA-sensitized mice respectively. Lung pathological scores were assessed by HE stain. Inflammatory cell infiltration and cytokine production were detected through BAL. The expression levels of phosphorylation of STAT1, STAT4, STAT6 in lung were measured by western blot. 

Results: It showed DClps could migrate to OVA-sensitized lung with higher efficiency than DCim. DClps other than DCim, when adoptively transferred via peritoneal, greatly improved lung pathological scores and alleviated airway inflammatory infiltration due to production of more IL-10 and TGF-β. Administration of BMDCs with/without SOCS3 gene pulsed with LPS before adoptive transfer, resulted in significant improvement of allergic airway inflammation. It is note interestingly that SOCS3-/-DC even slightly abolished BMDC-induced immunogenic tolerance. LPS-stimulated matured BMDCs were found to inhibit STAT4 and STAT6 signaling pathways in OVA-sensitized mice lung. 

Conculsion: BMDC adoptive transfer induced immunogenic tolerance in OVA-sensitized mice might not due to SOCS3 gene depletion. LPS-stimulated matured BMDC produced more IL-10 and TGF-β, leading to dramatic decrease both of phosphorylation of STAT4 and STAT6 expresion which are critical in initiating Th1 and Th2 mediated immunoinflammatory process in asthma. BMDC adoptive transfer might develop a new approach in the treatment of asthma by fine modulating the balance between immune tolerance and immnue inflammation.

刘晓静博士壁报摘要

Rationale: Interleukin-27 (IL-27) can modulate the CD4+ T cells differentiation and response, which is a critical process in the development of adaptive immune responses. We sought to investigate the possible preventative effect of IL-27 on asthma and explore the underlying mechanism.

Methods: We detected the effect of preventative intranasal administration of IL-27 in an ovalbumin (OVA) -induced mouse model. After harvesting lung mononuclear cells, different T helper (Th) cell classes were detected by fluorescence-activated cell sorting (FACS). Then we explored the effect of IL-27 on human bronchial epithelial (HBE) cells in vitro. The mRNA expression of chemotactic factors, cytokines and transcript factors were measured by real-time PCR. The expression of p-STAT1, GADD45γ and p-p38 MAPK were measured by western blot.

Results: Preventative intranasal administration of IL-27 attenuates airway inflammation and improves airway hyperreactivity (AHR) in an OVA-induced mouse model. And it can up-regulate Th1-T memory (Tm) and regulatory T (Treg) subgroups of mouse lung tissue lymphocytes and diminishes concentrations of Th2 cytokines. IL-27 up-regulates the expression of C-C motif chemokine ligand 2 (CCL2), CCL3 and CCL4 of HBE. The promoted secreted chemotactic factors recruit more U937 cells. And the recruited U937 can in return secret IL-27 to take effect on the HBE cells, which might form a positive feedback cycle. Finally, preventative IL-27’s effects were mediated by reversing the impairment of the signal transducer and activator of transcription 1 (STAT1) pathway or strengthening the GADD45γ/p38 MAPK pathway.

Conclusions: The HBE cells in the IL-27 environment can secret more chemotactic factors to recruit the mononuclear phagocyte system (MPS). The recruited MPS cells can in return secret IL-27 to take effect on the HBE cells, which might form a cycle. Preventative intranasal administration of IL-27 can promote naïve CD4+T cells differentiated into Th1 cells. The improved Th1 environment helps to alleviate Th2-mediated allergic asthma by repairing the STAT1 pathway and strengthening the GADD45γ/p38 MAPK pathway.

专题报道链接>>>2019年美国胸科学会年会

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