DHRS9是人类调节性巨噬细胞的稳定标志物。
DHRS9 Is a Stable Marker of Human Regulatory Macrophages.
作者信息
Riquelme Paloma, Amodio Giada, Macedo Camila, Moreau Aurelie, Obermajer Nataša, Brochhausen Christoph, Ahrens Norbert, Kekarainen Tuija, Fändrich Fred, Cuturi Cristina, Gregori Silvia, Metes Diana, Schlitt Hans J, Thomson Angus W, Geissler Edward K, Hutchinson James A
机构信息
1 Department of Surgery, University Hospital Regensburg, Regensburg, Germany. 2 San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Division of Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy. 3 Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA. 4 INSERM UMR1064, Center for Research in Transplantation and Immunology, Nantes, France. 5 CHU de Nantes, Institut de Transplantation Urologie Nephrologie (ITUN), Nantes, France. 6 Université de Nantes, Nantes, France. 7 Division of Surgical Oncology, University of Pittsburgh, Hillman Cancer Center, Pittsburgh, PA. 8 Institute of Pathology, University Hospital Regensburg, Regensburg, Germany. 9 Department of Transfusion Medicine, University Hospital Regensburg, Regensburg, Germany. 10 Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. 11 FinVector Vision Therapies Oy, Microkatu 1S, Kuopio, Finland. 12 Institute for Applied Cell Therapy, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
出版信息
Transplantation. 2017 Nov;101(11):2731-2738. doi: 10.1097/TP.0000000000001814.
BACKGROUND
The human regulatory macrophage (Mreg) has emerged as a promising cell type for use as a cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. In this brief report, dehydrogenase/reductase 9 (DHRS9) is identified as a robust marker of human Mregs.
METHODS
The cognate antigen of a mouse monoclonal antibody raised against human Mregs was identified as DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression of DHRS9 within a panel of monocyte-derived macrophages was investigated by quantitative PCR, immunoblotting and flow cytometry.
RESULTS
DHRS9 expression discriminated human Mregs from a panel of in vitro derived macrophages in other polarisation states. Likewise, DHRS9 expression distinguished Mregs from a variety of human monocyte-derived tolerogenic antigen-presenting cells in current development as cell-based immunotherapies, including Tol-DC, Rapa-DC, DC-10, and PGE2-induced myeloid-derived suppressor cells. A subpopulation of DHRS9-expressing human splenic macrophages was identified by immunohistochemistry. Expression of DHRS9 was acquired gradually during in vitro development of human Mregs from CD14 monocytes and was further enhanced by IFN-γ treatment on day 6 of culture. Stimulating Mregs with 100 ng/mL lipopolysaccharide for 24 hours did not extinguish DHRS9 expression. Dhrs9 was not an informative marker of mouse Mregs.
CONCLUSION
DHRS9 is a specific and stable marker of human Mregs.
背景
人类调节性巨噬细胞（Mreg）已成为一种有前景的细胞类型，可作为实体器官移植受者基于细胞的辅助免疫抑制疗法。在本简短报告中，脱氢酶/还原酶9（DHRS9）被鉴定为人类Mreg的一个可靠标志物。
方法
通过免疫沉淀和基质辅助激光解吸电离质谱测序，将针对人类Mreg产生的小鼠单克隆抗体的同源抗原鉴定为DHRS9。通过定量PCR、免疫印迹和流式细胞术研究了一组单核细胞衍生巨噬细胞中DHRS9的表达。
结果
DHRS9的表达可将人类Mreg与处于其他极化状态的一组体外衍生巨噬细胞区分开来。同样，DHRS9的表达也将Mreg与当前作为基于细胞的免疫疗法正在开发的多种人类单核细胞衍生的耐受性抗原呈递细胞区分开来，包括Tol-DC、Rapa-DC、DC-10和前列腺素E2诱导的髓源性抑制细胞。通过免疫组织化学鉴定出了表达DHRS9的人类脾脏巨噬细胞亚群。在人类Mreg从CD14单核细胞体外发育过程中，DHRS9的表达逐渐获得，并在培养第6天通过干扰素-γ处理进一步增强。用100 ng/mL脂多糖刺激Mreg 24小时并未消除DHRS9的表达。Dhrs9不是小鼠Mreg的一个有用标志物。
结论
DHRS9是人类Mreg的一个特异性且稳定的标志物。
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