title: M2 polarization of murine peritoneal macrophages induces regulatory cytokine production and suppresses T-cell proliferation.
abstract: Bone-marrow-derived macrophages are divided into two phenotypically and functionally distinct subsets, M1 and M2 macrophages. Recently, it was shown that adoptive transfer of M2-polarized peritoneal macrophages reduced the severity of experimental colitis in mice. However, it is still unclear whether peritoneal macrophages possess the same ability to be polarized to cells with functionally different phenotypes and cytokine production patterns as bone-marrow-derived macrophages. To address this question, we examined the ability of peritoneal macrophages to be polarized to the M1 and M2 phenotypes and determined the specific cytokine profiles of cells with each phenotype. We showed that peritoneal macrophages, as well as bone-marrow-derived macrophages, were differentiated into M1 and M2 phenotypes following stimulation with interferon-γ (IFN-γ) and interleukin-4 (IL-4)/IL-13, respectively. Following in vitro stimulation with lipopolysaccharide, M2-polarized peritoneal macrophages predominantly expressed T helper type 2 (Th2) cytokines and regulatory cytokines, including IL-4, IL-13, transforming growth factor-β and IL-10, whereas M1-polarized peritoneal macrophages expressed negligible amounts of Th1 and pro-inflammatory cytokines. ELISA showed that M2-polarized peritoneal macrophages produced significantly more IL-10 than M1-polarized peritoneal macrophages. Notably, M2-polarized peritoneal macrophages contributed more to the suppression of T-cell proliferation than did M1-polarized peritoneal macrophages. The mRNA expression of Th2 cytokines, including IL-4 and IL-13, increased in T-cells co-cultured with M2-polarized macrophages. Hence, our findings showed that M2 polarization of peritoneal macrophages induced regulatory cytokine production and suppressed T-cell proliferation in vitro, and that resident peritoneal macrophages could be used as a new adoptive transfer therapy for autoimmune/inflammatory diseases after polarization to the regulatory phenotype ex vivo.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Oishi
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takano
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tamura
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tani
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Moriya
authors.initials: M
authors.lastname: Iwaizumi
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hamaya
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Takagaki
authors.affiliation: Department of Health Science, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Seto
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Horii
authors.affiliation: Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Osawa
authors.affiliation: Centre for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. sugimken@hama-med.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology*; D005260:Female; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: M1 macrophage; M2 macrophage; adoptive transfer; peritoneal macrophage; regulatory cytokines