1. Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the lesional muscle but not skin of patients with dermatomyositis.
- Author
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Fujiyama, T., Ito, T., Ogawa, N., Suda, T., Tokura, Y., and Hashizume, H.
- Subjects
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DERMATOMYOSITIS , *INTERLEUKIN-4 , *CXCR4 receptors , *T cells , *MUSCLE cells , *GENE expression , *PATIENTS - Abstract
Dermatomyositis ( DM) and polymyositis ( PM) are collectively termed autoimmune myopathy. To investigate the difference between muscle- and skin-infiltrating T cells and to address their role for myopathy, we characterized T cells that were directly expanded from the tissues. Enrolled into this study were 25 patients with DM and three patients with PM. Muscle and skin biopsied specimens were immersed in c RPMI medium supplemented with interleukin ( IL)-2 and anti- CD3/ CD28 antibody-conjugated microbeads. The expanded cells were subjected to flow cytometry to examine their phenotypes. We analysed the cytokine concentration in the culture supernatants from the expanded T cells and the frequencies of cytokine-bearing cells by intracellular staining. There was non-biased in-vitro expansion of tissue-infiltrating CD4+ and CD8+ T cells from the muscle and skin specimens. The majority of expanded T cells were chemokine receptor ( CCR) type 7- CD45 RO+ effecter memory cells with various T cell receptor ( TCR) Vβs. The skin-derived but not muscle-derived T cells expressed cutaneous lymphocyte antigen ( CLA) and CCR10 and secreted large amounts of IL-17 A, suggesting that T helper type 17 ( Th17) cells may have a crucial role in the development of skin lesions. Notably, the frequency of IL-4-producing chemokine (C-X-C motif) receptor (CX CR)4+ Th2 cells was significantly higher in the muscle-derived cells and correlated inversely with the serum creatine phosphokinase (CPK) and lactate dehydrogenase ( LDH) levels. stromal-derived factor (SDF)-1/ CXCL12, a ligand for CXCR4, was expressed at a high level in the vascular endothelial cells between muscular fasciculi. Our study suggests that T cell populations in the muscle and skin are different, and the Th2 cell infiltrate in the muscle is associated with the low severity of myositis in DM. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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