Th2‐M2 immunity in lesions of muscular sarcoidosis and macrophagic myofasciitis

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 ( T h)1 inducing classical macrophage activation (e.g. STAT 1, IFN γ and CXCR 3), and T h2 inducing alternative activation of macrophages (e.g. CD 206/ MRC 1, STAT 6, SOCS 1), molecules involved in development of fibrosis (e.g. TGF β) and giant cells (e.g. TYROBP ), were assessed by immunohistochemistry and real‐time polymerase chain reaction ( PCR ). Results STAT 6‐induced T h2 immunity was associated with up‐regulated gene expression of MRC 1 , SOCS 1 and TGFB in inflammatory foci, in comparison with adjacent tissue. TYROBP and TREM 2 , genes regulating giant cell formation, were more strongly expressed in lesions of MuS patients than in those of MMF . TGF β co‐localized with CD 206 + macrophages in MuS but not in MMF . Conversely, T h1 immunity was illustrated by STAT 1 staining both in macrophages and myofibres in MuS , but not in MMF . Also, STAT 1‐induced IFNG and CXCR 3 expression in lesions and the surrounding tissue was elevated compared with normal controls, but without statistically significant differences. Conclusion Giant cell and typical granuloma formations, including fibrogenesis, is dependent on two main mechanisms, both involving specific macrophage activation: a strong T h2‐ M 2 polarization and a significant expression of TYROBP and TGF β in macrophages. The low‐grade alternative activation of macrophages in MMF lesions and poor TYROBP and TGF βco‐expression are obviously insufficient to produce giant cells.