Transfusion of CD206+ M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice

• Published in: The American journal of pathology Vol. 186; no. 12; pp. 3176 - 3188
• Main Authors: Du, Qiuna, Tsuboi, Naotake, Shi, Yiqin, Ito, Sachiko, Sugiyama, Yutaka, Furuhashi, Kazuhiro, Endo, Nobuhide, Kim, Hangsoo, Katsuno, Takayuki, Akiyama, Shin'ichi, Matsuo, Seiichi, Isobe, Ken-Ichi, Maruyama, Shoichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016
• Subjects: Animals; Antibodies - adverse effects; Coculture Techniques; Cytokines - immunology; Cytokines - metabolism; Disease Models, Animal; Glomerulonephritis - immunology; Glomerulonephritis - physiopathology; Glomerulonephritis - therapy; Humans; Kidney - immunology; Kidney - physiopathology; Kidney Glomerulus - immunology; Kidney Glomerulus - physiopathology; Lectins, C-Type - immunology; Lymph Nodes - immunology; Lymph Nodes - physiopathology; Macrophages - immunology; Macrophages - transplantation; Male; Mannose-Binding Lectins - immunology; Mice; Mice, Inbred C57BL; Pathology; Receptors, Cell Surface - immunology; Spleen - immunology; Spleen - physiopathology; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2016.08.012

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.