DHRS9 Is a Stable Marker of Human Regulatory Macrophages

Paloma Riquelme 1, * Giada Amodio 2 Camila Macedo 3 Aurélie Moreau 4, 5, 6 Nataša Obermajer 7 Christoph Brochhausen 8 Norbert Ahrens 9 Tuija Kekarainen 10, 11 Fred Fändrich 12 Cristina Cuturi 4, 5, 6 Silvia Gregori 2 Diana Metes 3 Hans Schlitt 1 Angus Thomson 3 Edward Geissler 1 James Hutchinson 1
* Corresponding author
1 Department of Surgery, Section of Experimental Surgery [Regensburg, Germany]
2 Division of Regenerative Medicine, Stem Cells and Gene Therapy [Milan, Italy]
3 Thomas E. Starzl Transplantation Institute - Department of Surgery [Pittsburgh, PA, USA]
4 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
5 ITUN - Institut de transplantation urologie-néphrologie
6 Faculté de Médecine - Université de Nantes
7 Hillman Cancer Center - Division of Surgical Oncology [Pittsburgh, PA, USA]
8 Institute of Pathology [Regensburg, Germany]
9 Department of Transfusion Medicine [Regensburg, Germany]
10 A.I. Virtanen Institute for Molecular Sciences - Department of Biotechnology and Molecular Medicine [Kuopio, Finland]
11 FinVector Vision Therapies Oy [Kuopio, Finland]
12 Campus Kiel - Institute for Applied Cell Therapy [Kiel, Germany]
Abstract : 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 PGE 2-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.
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Paloma Riquelme, Giada Amodio, Camila Macedo, Aurélie Moreau, Nataša Obermajer, et al.. DHRS9 Is a Stable Marker of Human Regulatory Macrophages. Transplantation, Lippincott, Williams & Wilkins, 2017, 101 (11), pp.2731-2738. ⟨10.1097/TP.0000000000001814⟩. ⟨inserm-02154878⟩

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