title: Neonatal lymph node stromal cells drive myelodendritic lineage cells into a distinct population of CX3CR1+CD11b+F4/80+ regulatory macrophages in mice.
abstract: Beyond providing a scaffold for immune cells, recent studies indicate that lymph node stromal cells provide potent regulatory capacities that affect the quality of adaptive immune responses. In this study, we provide evidence that neonatal lymph node stromal cells (nnLNSCs) consistently promote the differentiation of macrophage dendritic cell progenitors as well as mature and immature dendritic cells into a distinct population of CX3CR1(+) CD11b(+)F4/80(+) regulatory macrophages (regMΦ). These cells possess remarkably low levels of T cell costimulatory molecules as well as MHC class II molecules. regMΦ do not interfere with early T-cell activation but, via nitric oxide secretion, efficiently suppress T-cell proliferation. Furthermore, CD4(+) T cells proliferating in the presence of regMΦ gain immunosuppressive capacity and MΦ isolated from day 3 nnLNs are T-cell immunosuppressive. Adoptive transfer of antigen-loaded regMΦ induce a profound antigen-specific immune suppression in vivo. Together our data show that nnLNSCs skew the differentiation of dendritic cells and their progenitors toward regMΦ, thus revealing a novel mechanism for local immune regulation.
authors.affiliation: Institute of Immunology, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover, Germany.
authors.forename: Xiangyue
authors.initials: X
authors.lastname: Zhang
authors.forename: Songfeng
authors.initials: S
authors.lastname: Yu
authors.forename: Katharina
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018122:B7-1 Antigen / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010641:Phenotype; D019707:Receptors, Chemokine / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D000949:Histocompatibility Antigens Class II; D019707:Receptors, Chemokine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II