Unknown

Dataset Information

0

IFN-?-induced iNOS expression in mouse regulatory macrophages prolongs allograft survival in fully immunocompetent recipients.


ABSTRACT: Mouse monocytes exposed to macrophage colony-stimulating factor (M-CSF) and interferon-? (IFN-?) 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 × 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.

SUBMITTER: Riquelme P 

PROVIDER: S-EPMC3594012 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

| GSE32690 | GEO
2013-12-21 | E-GEOD-32690 | ArrayExpress
2011-01-01 | S-EPMC3776382 | BioStudies
2020-01-01 | S-EPMC6971488 | BioStudies
1000-01-01 | S-EPMC2118630 | BioStudies
2012-01-01 | S-EPMC3561050 | BioStudies
2018-01-01 | S-EPMC6351502 | BioStudies
2019-01-01 | S-EPMC6519070 | BioStudies
2011-01-01 | S-EPMC3208127 | BioStudies
2012-01-01 | S-EPMC3762575 | BioStudies