title: Co-culture of spleen stromal cells with bone marrow mononuclear cells leads to the generation of a novel macrophage subset.
abstract: Macrophages adopt diverse activation states depending on the microenvironment. Recently, stromal cells have been demonstrated to be organizers of the microenvironment. Here, using splenic stromal cells to mimic the splenic microenvironment in vivo, we show that spleen stromal cells can programme bone marrow-derived mononuclear cells to differentiate and polarize into a novel macrophage subset. These differentiated macrophages (Diff-Mφ) exhibited pronounced production of IL-10, IL-6 and TNF-α, but diminished the production of IL-12 in response to LPS. The generation of Diff-Mφ depended on cell-cell contact as well as on soluble factors. Diff-Mφ directly suppressed the antigen-non-specific (CD3/CD28) CD4(+) T cell proliferative response and induced cell death of activated CD4(+) T cells. As for cytokine production in CD4(+) T cells, Diff-Mφ promoted IL-10 and IL-17 production, whereas inhibited IL-4 production and did not alter IFN-γ production. Besides, Diff-Mφ also expressed iNOS, CD16/CD32, CD54, CD43, CCR7, CD44, PD-L1 and FasL, which might be involved in the function of Diff-Mφ. These results suggest that splenic microenvironment may physiologically induce a novel type of macrophages differentiation.
authors: Research Center of Molecular Biology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China; Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors: X
authors: X
authors: Wang
authors: Y
authors: Y
authors: Li
authors: H
authors: H
authors: Xiao
authors: X
authors: X
authors: Zhang
authors: J
authors: J
authors: Cao
authors: D
authors: D
authors: Zhang
authors: J
authors: J
authors: Zhang
authors: X
authors: X
authors: Li
authors: B
authors: B
authors: Shen
authors: Q
authors: Q
authors: Wang
authors: Y
authors: Y
authors: Shi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II