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修复后的单核细胞具有免疫调节作用，并调节脓毒症中的炎症环境。

Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis.

机构信息

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.

Department of Medicine, Dr. Ram Mahohar Lohia Hospital, Baba Kharak Singh Road, New Delhi, 110001, India.

出版信息

Sci Rep. 2023 Sep 11;13(1):14977. doi: 10.1038/s41598-023-42237-4.

DOI:10.1038/s41598-023-42237-4
PMID:37696985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10495550/
Abstract

Sepsis is caused by dysregulated immune response to severe infection and hyper inflammation plays a central role in worsening the disease. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been evaluated as a therapeutic candidate for sepsis. Reconditioned monocytes (RM), generated from healthy human peripheral blood mononuclear cells (PBMCs) exhibit both macrophage and MSCs-like properties. RM were administered at different stages of sepsis in a mouse model. It reduced serum levels of IL6, MCP-1, IL-10, improved hypothermia, increased survival, and recovery from 0 to 66% when combined with antibiotics in the mouse model. The reduced human leucocyte antigen DR molecules expression on RM enables their co-culture with PBMCs of sepsis patients which resulted in reduced ROS production, and up-regulated TGF-β while down-regulating IL6, IL8, and IL-10 in-vitro. RM are potentially immunomodulatory, enhance survival in sepsis mouse model and modulate inflammatory behaviour of sepsis patient's PBMCs.

摘要

脓毒症是由严重感染引起的免疫反应失调和过度炎症引起的，在疾病恶化中起着核心作用。间充质干细胞（MSCs）的免疫调节特性已被评估为脓毒症的治疗候选物。从健康人外周血单核细胞（PBMC）中产生的再调理单核细胞（RM）表现出巨噬细胞和 MSC 样特性。在小鼠模型中，RM 在脓毒症的不同阶段给药。它降低了血清中白细胞介素 6（IL6）、单核细胞趋化蛋白 1（MCP-1）、白细胞介素 10（IL-10）的水平，当与抗生素联合使用时，提高了体温、存活率并从 0 恢复到 66%。RM 上 HLA-DR 分子表达的减少使其能够与脓毒症患者的 PBMC 共培养，这导致 ROS 产生减少，TGF-β上调，同时下调 IL6、IL8 和 IL-10。RM 具有潜在的免疫调节作用，可提高脓毒症小鼠模型的存活率，并调节脓毒症患者 PBMC 的炎症行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/4386325f0fe3/41598_2023_42237_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/413e4a58b8ba/41598_2023_42237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/362ed85e0c45/41598_2023_42237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/263037fa3b12/41598_2023_42237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/159c328e9704/41598_2023_42237_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/89a2356a3c5b/41598_2023_42237_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/4386325f0fe3/41598_2023_42237_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/413e4a58b8ba/41598_2023_42237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/362ed85e0c45/41598_2023_42237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/263037fa3b12/41598_2023_42237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/159c328e9704/41598_2023_42237_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/89a2356a3c5b/41598_2023_42237_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc2f/10495550/4386325f0fe3/41598_2023_42237_Fig6_HTML.jpg

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