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Novel molecules mediate specialized functions of human regulatory macrophages

Riquelme, Paloma; Hutchinson, James A.

Current Opinion in Organ Transplantation: October 2018 - Volume 23 - Issue 5 - p 533–537
doi: 10.1097/MOT.0000000000000560
REGULATORY IMMUNE CELLS IN ORGAN TRANSPLANTATION AND THEIR THERAPEUTIC APPLICATION: Edited by Angus W. Thomson
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Purpose of review Now that adoptive transfer of regulatory macrophages (Mregs) is clinically practicable, we ask whether this approach could be used to achieve self-sustaining peripheral regulation and what mechanisms may be involved.

Recent findings Dehydrogenase/reductase 9 (DHRS9)-expressing Mregs are a specialized subset of monocyte-derived macrophages that are currently being investigated as a tolerogenic cell-based therapy. Human Mregs are defined by their capacity to convert naïve CD4+ T cells to IL-10-secreting FoxP3+ regulatory T cells (Tregs) through an activation-dependent process involving signals mediated by TGF-β, retinoic acid, indoleamine 2,3-dioxygenase activity, notch and progestagen associated endometrial protein (PAEP). Mreg-induced iTregs (miTregs) are a phenotypically distinct type of in-vitro-derived human iTreg that expresses butyrophilin-like protein 8 (BTNL8) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). miTregs are nonspecifically suppressive of mitogen-stimulated bystander T cell proliferation and inhibit TNFα-induced maturation of monocyte-derived dendritic cells. Preclinical and clinical studies find that intravenous infusion of allogeneic Mregs leads to enrichment of circulating TIGIT+ Tregs.

Summary These results suggest a feed-forward mechanism by which Mreg treatment could promote solid organ transplant acceptance through rapid induction of direct pathway Tregs.

Department of Surgery, University Hospital Regensburg, Regensburg, Germany

Correspondence to Paloma Riquelme, Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Tel: +49 941 944 4878; fax: +49 941 944 6772; e-mail: paloma.riquelme@ukr.de

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