Riquelme, Paloma and Hutchinson, James A. (2018) Novel molecules mediate specialized functions of human regulatory macrophages. CURRENT OPINION IN ORGAN TRANSPLANTATION, 23 (5). pp. 533-537. ISSN 1087-2418, 1531-7013
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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 naive CD4(+) T cells to IL-10-secreting FoxP3(+) regulatory T cells (Tregs) through an activation-dependent process involving signals mediated by TGF-beta, 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 TNF alpha-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLYCODELIN-A; CELLS; EXPRESSION; INDUCTION; TOLERANCE; MECHANISM; MONOCYTES; THERAPY; CHAIN; BTNL8; cell-based therapy; DHRS9; induced Treg; miTreg; PAEP; regulatory macrophage; solid organ transplantation; TIGIT |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Petra Gürster |
| Date Deposited: | 14 Jul 2020 10:52 |
| Last Modified: | 14 Jul 2020 10:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13721 |
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