Mast cells contribute to muscle regeneration, yet not inflammation in murine myositis = Mast cells contribute to muscle regeneration, yet not inflammation in murine myositis

다국어 초록 (Multilingual Abstract)

Background: Mast cells (MCs) function as immune sentinel cells in the tissue. The well-known cellular infiltrate in inflammatory myositis mainly consists of macrophages and lymphocytes that produce numerous inflammatory cytokines and chemokines augmenting inflammatory cell infiltration and damage of myofibers. The role of tissue-resident MCs has not been well studied in inflammatory myositis. We aimed to study the phenotype and role of MCs in a murine myositis model. Methods: C-protein induced myositis (CIM) was induced in MC-deficient SASH mice and controls (C57BL/6). Tissue inflammation was evaluated in hematoxylin & eosin (H&E) stained sections via a scoring system of 0 3. Immunohistochemistry (IHC) of mouse MC protease (mMCP) -1, -4, -5, -6, CD8 and measurement of serum TNF-α, IL-1β, IL-6, IFN-γ, IL-10 were performed. Total MC density and degranulating MCs was enumerated in 5 high power fields in CIM and control tissues stained with toluidine blue. Inflammatory infiltrates and regeneration muscle fibers were counted in CIM tissue stained with H&E. Regeneration muscle marker Mi-2 was assessed in CIM tissue by IHC. Results: Total MC density was significantly increased in CIM tissues compared with healthy mice (35.2 ± 2.3 versus (vs.) 18.0 ± 2.4, p＝0.028), as well as degranulating MCs (17.5 ± 5.0 vs. 3.3 ± 1.9, p＝0.029). However, there was no difference in muscle inflammation between CIM induced SASH mice and CIM induced controls (histology score 1.39 ± 0.17 vs. 1.60 ± 0.15). Serum level of IL-6 was slightly decreased in SASH compared with controls (35.1 ± 9.1 vs. 59.5 ± 12.0 pg/mL, p＝0.09). Serum levels of TNF-α, IL-1β and IFN-γwere not significantly different between the 2 groups. Yet, infiltration of CD8 positive cells in inflamed muscle fibers was decreased in SASH compared to controls (6.4 ± 0.8 vs. 2.1 ± 0.5, p 0.0001), the same loci where Mi-2 positive fibers were also significantly decreased (SASH CIM, 2.4 ± 0.5 vs. control CIM, 10.58 ±2.0, p 0.0002). Conclusions: The connective tissue-type MCs in skeletal muscles are activated upon CIM induction. The MCs do not engage in inducing robust muscle inflammation, but play a role in muscle regeneration.