title: Th2-M2 immunity in lesions of muscular sarcoidosis and macrophagic myofasciitis.
abstract: OBJECTIVE
  To analyse the paradox of a lack of giant cell formation and fibrosis in chronic lesions of macrophagic myofasciitis (MMF) in comparison with muscular sarcoidosis (MuS).
  
  
  METHODS
  Inflammatory lesions and contiguous muscle regions from biopsy samples of 10 patients with MuS and 10 patients with MMF were cut out by laser microdissection. Mediators of the T helper cell (Th)1 inducing classical macrophage activation (e.g. STAT1, IFNγ and CXCR3), and Th2 inducing alternative activation of macrophages (e.g. CD206/MRC1, STAT6, SOCS1), molecules involved in development of fibrosis (e.g. TGFβ) and giant cells (e.g. TYROBP), were assessed by immunohistochemistry and real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  STAT6-induced Th2 immunity was associated with up-regulated gene expression of MRC1, SOCS1 and TGFB in inflammatory foci, in comparison with adjacent tissue. TYROBP and TREM2, genes regulating giant cell formation, were more strongly expressed in lesions of MuS patients than in those of MMF. TGFβ co-localized with CD206(+) macrophages in MuS but not in MMF. Conversely, Th1 immunity was illustrated by STAT1 staining both in macrophages and myofibres in MuS, but not in MMF. Also, STAT1-induced IFNG and CXCR3 expression in lesions and the surrounding tissue was elevated compared with normal controls, but without statistically significant differences.
  
  
  CONCLUSIONS
  Giant cell and typical granuloma formations, including fibrogenesis, is dependent on two main mechanisms, both involving specific macrophage activation: a strong Th2-M2 polarization and a significant expression of TYROBP and TGFβ in macrophages. The low-grade alternative activation of macrophages in MMF lesions and poor TYROBP and TGFβco-expression are obviously insufficient to produce giant cells.
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Preusse
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.|Department of Neuropathology, University Medicine, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Goebel
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Debora
authors.initials: D
authors.lastname: Pehl
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Rinnenthal
authors.affiliation: Department of Neurology, Neuromuscular Center Ruhrgebiet, University Hospital Bergmannsheil, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Kley
authors.affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence Maladies Neuro-Musculaires Paris Est, Assistance Public - Hôpitaux de Paris (AP-HP), DHU I2B, Paris, France.|Université Pierre et Marie Curie (UPMC), INSERM UMRS 974, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allenbach
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.affiliation: Department of Neurology, Neuromuscular Center Ruhrgebiet, University Hospital Bergmannsheil, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.affiliation: Neuromuscular Pathology Expert Center, Henri Mondor Hospital, Creteil, and INSERM U955, Faculty of Medicine, Paris Est University, Creteil, France.
authors.forename: François Jerôme
authors.initials: FJ
authors.lastname: Authier
authors.affiliation: Neuromuscular Pathology Expert Center, Henri Mondor Hospital, Creteil, and INSERM U955, Faculty of Medicine, Paris Est University, Creteil, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Gherardi
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
mesh_terms: D000328:Adult; D000368:Aged; D005208:Fasciitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D009220:Myositis / Q000276:immunology* / Q000473:pathology; D012507:Sarcoidosis / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
keywords: immunology; laser microdissection; macrophagic myofasciitis; muscle disease; neuromuscular sarcoidosis