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急性胰腺炎患者中具有抑制功能增强的髓源性抑制细胞。

Myeloid-Derived Suppressor Cells in Patients With Acute Pancreatitis With Increased Inhibitory Function.

机构信息

Intensive Care Unit, The First Hospital of Jilin University, Changchun, China.

Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

Front Immunol. 2022 Jul 14;13:840620. doi: 10.3389/fimmu.2022.840620. eCollection 2022.

DOI:10.3389/fimmu.2022.840620
PMID:35911709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9329796/
Abstract

Acute pancreatitis (AP) is pancreatic or systemic inflammation without or with motion organ dysfunction. Severe acute pancreatitis (SAP) is the main cause of death for patients with AP. A pro-/anti-inflammatory imbalance is considered the key regulation of disease severity. However, the real mechanism of SAP remains unclear. This study aimed to identify the frequency and specific roll of myeloid-derived suppressor cell (MDSC) in AP. We evaluated MDSC frequency and disease severity by analyzing MDSCs in the peripheral blood of healthy controls (HCs) and patients with mild acute pancreatitis (MAP) and SAP by flow cytometry. We also compared the frequency and inhibitory ability of MDSCs from HCs and SAP, and finally detected the reason for the difference in inhibitory ability. AP was marked by expansion of MDSCs as well as its subsets, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). The proportion of MDSC in the peripheral blood mononuclear cells of patients with AP was increased and positively correlated with AP severity. The frequency of MDSC was decreased after treatment compared with pre-treatment. CD3+ T cells were remarkably inhibited by MDSC derived from the patients with SAP. In the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), the MDSCs from patients with SAP increased. These findings demonstrated that MDSCs expanded in the peripheral blood in patients with AP, especially in those with SAP. Moreover, the inhibitory ability of MDSCs was increased in the patients with SAP compared with that in the HCs. The enhanced suppressive function was possibly caused by an overexpression of Arg-1 and ROS.

摘要

急性胰腺炎(AP)是一种无或伴有运动器官功能障碍的胰腺或全身炎症。重症急性胰腺炎(SAP)是 AP 患者死亡的主要原因。促炎/抗炎失衡被认为是疾病严重程度的关键调节因素。然而,SAP 的真正机制仍不清楚。本研究旨在确定髓系来源的抑制细胞(MDSC)在 AP 中的频率和特定作用。我们通过流式细胞术分析健康对照(HCs)和轻度急性胰腺炎(MAP)和 SAP 患者外周血中的 MDSC,评估 MDSC 的频率和疾病严重程度。我们还比较了 HCs 和 SAP 中 MDSC 的频率和抑制能力,并最终检测了抑制能力差异的原因。AP 的特征是 MDSC 及其亚群、粒细胞 MDSC(G-MDSC)和单核细胞 MDSC(M-MDSC)的扩张。AP 患者外周血单个核细胞中 MDSC 的比例增加,并与 AP 的严重程度呈正相关。与治疗前相比,治疗后 MDSC 的频率降低。SAP 患者来源的 MDSC 显著抑制 CD3+T 细胞。在精氨酸酶-1(Arg-1)和活性氧(ROS)的表达中,SAP 患者的 MDSC 增加。这些发现表明,AP 患者外周血中 MDSC 扩张,尤其是 SAP 患者。此外,SAP 患者的 MDSC 抑制能力高于 HCs。增强的抑制功能可能是由于 Arg-1 和 ROS 的过度表达所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/8b5c14ffa417/fimmu-13-840620-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/b40e6139464c/fimmu-13-840620-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/fac35d81a141/fimmu-13-840620-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/da8c172920d0/fimmu-13-840620-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/487a3d25fe5c/fimmu-13-840620-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/8b5c14ffa417/fimmu-13-840620-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/b40e6139464c/fimmu-13-840620-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/58daaa500a88/fimmu-13-840620-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/9b0c190f4a9f/fimmu-13-840620-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/7d6385050c50/fimmu-13-840620-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/fac35d81a141/fimmu-13-840620-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/da8c172920d0/fimmu-13-840620-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/487a3d25fe5c/fimmu-13-840620-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6019/9329796/8b5c14ffa417/fimmu-13-840620-g008.jpg

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