P.21.3 Skeletal muscle provides a permissive environment for Th2-M2 polarisation in neuromuscular sarcoidosis

Abstract

Neuromuscular involvement may affect more then 60% of patients suffering from sarcoidosis. We have recently described that macrophages and giant cells in skeletal muscle exhibit an unexpected status of alternative activation (M2). Objective: The intrinsic immune signature of the granulomas, was compared to the cytokine profile of adjacent non-inflamed muscle tissue and to healthy control muscle. Granulomas and contiguous muscle from 9 patients with biopsy-proven neuromuscular sarcoidosis were cut out by laser capture microdissection (LCM). Markers and activators of the T helper cell 1 (Th1) – classical macrophage activation (M1) and Th2 – alternatively activated (M2) immune response as well as molecules involved in giant cell development were assessed by real-time PCR. STAT-6-induced Th2 immunity leads to upregulated expression of CD206 and SOCS1 in the granuloma in comparison to adjacent tissue. DAP12 and RAC1, genes that regulate giant cell formation, are significantly induced in the granulomas. Conversely, STAT-1-induced Th1 immunity, IFN γ and CXCR3 are expressed in the granulomas and the surrounding tissue at elevated levels, however without statistical differences. While Th1-mediated immunity is upregulated in the whole inflamed muscle specimen, Th2-M2 markers are expressed at significantly higher levels in the granulomata. These results indicate that muscle tissue per se may provide a permissive environment for M2 polarisation in neuromuscular sarcoidosis.