title: Transfusion of CD206+M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice.
abstract: Macrophages are multifunctional immune cells that may either drive or modulate disease pathogenesis, depending on the activated phenotype. In this study, we investigated the protective effects of CD206+M2 macrophages against nephrotoxic serum nephritis in mice. We found that these immunosuppressive macrophages, derived from bone marrow and stimulated with IL-4/IL-13 [CD206+M2 bone marrow-derived macrophages (M2BMMs)], protected against renal injury, decreased proteinuria, and diminished the infiltration of CD68+macrophages, neutrophils, and T cells into glomerular tissue. Comparable therapeutic results were obtained with CD206+M2 cells derived from induced pluripotent stem cells. Notably, CD206+M2BMMs, which retained an M2 signature, could elicit a switch of M1 to M2 phenotype in co-cultured macrophages. Moreover, these cells were found to induce the production of regulatory T cells in the spleen and renal draining lymph node. Accordingly, mRNA expression of the T helper 1 cytokines tumor necrosis factor-α, interferon-β, interferon-γ, and IL-12 was significantly reduced in kidneys from mice treated with CD206+M2BMMs. Taken together, the data suggest that CD206+M2 may have therapeutic potential against antibody-mediated glomerular injury and presents its therapeutic value for the treatment of crescentic nephritis in humans.
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Qiuna
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: tsubotake05@med.nagoya-u.ac.jp.
authors.forename: Naotake
authors.initials: N
authors.lastname: Tsuboi
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Internal Medicine, and Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Medicine, Surgery, and Microbiology/Immunology, Columbia Center for Translational Immunology, College of Physicians and Surgeons, Columbia University, New York, New York.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furuhashi
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Endo
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hangsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Katsuno
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Akiyama
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.affiliation: Department of Internal Medicine, and Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Isobe
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000906:Antibodies / Q000009:adverse effects*; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000503:physiopathology; D037181:Lectins, C-Type / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000503:physiopathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface