Riquelme, Paloma and Tomiuk, Stefan and Kammler, Anja and Faendrich, Fred and Schlitt, Hans J. and Geissler, Edward K. and Hutchinson, James A. (2013) IFN-gamma-induced iNOS Expression in Mouse Regulatory Macrophages Prolongs Allograft Survival in Fully Immunocompetent Recipients. MOLECULAR THERAPY, 21 (2). pp. 409-422. ISSN 1525-0016, 1525-0024
Full text not available from this repository. (Request a copy)Abstract
Mouse monocytes exposed to macrophage colony-stimulating factor (M-CSF) and interferon-gamma (IFN-gamma) were driven to a novel suppressor phenotype. These regulatory macrophages (M regs) expressed markers distinguishing them from M0-, M1-, and M2-polarized macrophages and monocyte-derived dendritic cells (DCs). M regs completely suppressed polyclonal T cell proliferation through an inducible nitric oxide synthase (iNOS)-dependent mechanism. Additionally, M regs eliminated cocultured T cells in an allospecific fashion. In a heterotopic heart transplant model, a single intravenous administration of 5 x 10(6) donor-strain M regs before transplantation significantly prolonged allograft survival in fully immunocompetent recipients using both the stringent C3H-to-BALB/c (32.6 +/- 4.5 versus 8.7 +/- 0.2 days) and B6-to-BALB/c (31.1 +/- 12 versus 9.7 +/- 0.4 days) strain combinations. Nos2-deficient M regs did not prolong allograft survival, proving that M reg function in vivo is iNOS-dependent and mediated by living cells. M regs were detectable for at least 2 weeks postinfusion in allogeneic recipients. In their origin, development, phenotypic relationship with other in vitro-derived macrophages and functions, there are solid grounds to assert a near-equivalence of mouse and human M regs. It is concluded that mouse M regs represent a novel, phenotypically distinct subset of suppressor macrophages. Clinical applications of M reg therapy as an adjunct immunosuppressive therapy are currently being investigated within The ONE Study.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ISCHEMIA-REPERFUSION INJURY; RENAL-TRANSPLANT TOLERANCE; T-CELLS; DENDRITIC CELLS; MARGINAL ZONE; NITRIC-OXIDE; INDUCTION; MECHANISMS; ANTIGEN; DIFFERENTIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Apr 2020 05:22 |
| Last Modified: | 27 Apr 2020 05:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17208 |
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