TY - JOUR
T1 - Transfusion of CD206+ M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice
AU - Du, Qiuna
AU - Tsuboi, Naotake
AU - Shi, Yiqin
AU - Ito, Sachiko
AU - Sugiyama, Yutaka
AU - Furuhashi, Kazuhiro
AU - Endo, Nobuhide
AU - Kim, Hangsoo
AU - Katsuno, Takayuki
AU - Akiyama, Shin'ichi
AU - Matsuo, Seiichi
AU - Isobe, Ken Ichi
AU - Maruyama, Shoichi
N1 - Publisher Copyright:
© 2016 American Society for Investigative Pathology
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2016.08.012
DO - 10.1016/j.ajpath.2016.08.012
M3 - Article
C2 - 27855848
AN - SCOPUS:84995916402
SN - 0002-9440
VL - 186
SP - 3176
EP - 3188
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 12
ER -