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Chemokine profile of different inflammatory myopathies reflects humoral versus cytotoxic immune responses

Boel De Paepe (UGent) , Kim Creus (UGent) and Jan De Bleecker (UGent)
Author
Organization
Abstract
The idiopathic inflammatory myopathies (IM) are subdivided into dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (1BM). These autoimmune muscle diseases represent different immunopathological entities. DM is a Immoral endotheliopathy initiated by complement deposition in intramuscular blood vessels, and characterized by perimysial inflammation and muscle fiber atrophy in perifascicular regions. In PM and IBM, nonnecrotic muscle fibers are actively invaded by autoaggressive macrophages and cytotoxic T cells. Chemokines are key mediators of inflammatory disease as they regulate leukocyte recruitment to tissue target sites. We studied a large selection of alpha/beta-chemokines and receptors in normal controls and in the IM using immunohistochemistry, immunofluorescence, in situ hybridization, and Western blotting. We showed that the chemokine array of normal myocytes was limited, while the blood vessels in normal skeletal muscle tissue displayed a broad chemokine profile. The IM were characterized by a general increase of specific chemokines and chemokine receptors, while chemokine distribution reflected the two different immune responses represented within these muscle diseases. In DM, endothelial expression of CCL2 and CXCL12 beta was highly increased. In PM and IBM, macrophages and cytotoxic T cells actively invading nonnecrotic muscle fibers expressed highest levels of CXCL10 and CCL2. Some chemokines were selectively expressed by different IM infiltrates: CCL4 was present only in the perimysial inflammatory foci of a subset of DM biopsies, while CXCL1, CXCL2, CXCL3, and CCL7-positive cells were exclusively detected in endomysial infiltrates of a number of PM and IBM samples. The chemokine receptor profile of the IM indicated the predominance of Thl mediated immune responses in all three IM. Our studies identified three ligand-receptor pairs, namely CXCL10/CXCR3, CXCL12/CXCR4, and CCL2/CCR2, as potential targets for chemokine-based therapy in IM.
Keywords
inflammatory myopathy, dermatomyositis, polymyositis, inclusion body myositis, chemokines, chemokine receptors, INCLUSION-BODY MYOSITIS, RECEPTOR EXPRESSION, BETA-CHEMOKINES, CXCR3 LIGANDS, DERMATOMYOSITIS, MUSCLE, CELLS, POLYMYOSITIS, CYTOKINES, ALPHA

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Chicago
De Paepe, Boel, Kim Creus, and Jan De Bleecker. 2007. “Chemokine Profile of Different Inflammatory Myopathies Reflects Humoral Versus Cytotoxic Immune Responses.” Annals of the New York Academy of Sciences 1109: 441–453.
APA
De Paepe, Boel, Creus, K., & De Bleecker, J. (2007). Chemokine profile of different inflammatory myopathies reflects humoral versus cytotoxic immune responses. Annals of the New York Academy of Sciences, 1109, 441–453.
Vancouver
1.
De Paepe B, Creus K, De Bleecker J. Chemokine profile of different inflammatory myopathies reflects humoral versus cytotoxic immune responses. Annals of the New York Academy of Sciences. 2007;1109:441–53.
MLA
De Paepe, Boel, Kim Creus, and Jan De Bleecker. “Chemokine Profile of Different Inflammatory Myopathies Reflects Humoral Versus Cytotoxic Immune Responses.” Annals of the New York Academy of Sciences 1109 (2007): 441–453. Print.
@article{385368,
  abstract     = {The idiopathic inflammatory myopathies (IM) are subdivided into dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (1BM). These autoimmune muscle diseases represent different immunopathological entities. DM is a Immoral endotheliopathy initiated by complement deposition in intramuscular blood vessels, and characterized by perimysial inflammation and muscle fiber atrophy in perifascicular regions. In PM and IBM, nonnecrotic muscle fibers are actively invaded by autoaggressive macrophages and cytotoxic T cells. Chemokines are key mediators of inflammatory disease as they regulate leukocyte recruitment to tissue target sites. We studied a large selection of alpha/beta-chemokines and receptors in normal controls and in the IM using immunohistochemistry, immunofluorescence, in situ hybridization, and Western blotting. We showed that the chemokine array of normal myocytes was limited, while the blood vessels in normal skeletal muscle tissue displayed a broad chemokine profile. The IM were characterized by a general increase of specific chemokines and chemokine receptors, while chemokine distribution reflected the two different immune responses represented within these muscle diseases. In DM, endothelial expression of CCL2 and CXCL12 beta was highly increased. In PM and IBM, macrophages and cytotoxic T cells actively invading nonnecrotic muscle fibers expressed highest levels of CXCL10 and CCL2. Some chemokines were selectively expressed by different IM infiltrates: CCL4 was present only in the perimysial inflammatory foci of a subset of DM biopsies, while CXCL1, CXCL2, CXCL3, and CCL7-positive cells were exclusively detected in endomysial infiltrates of a number of PM and IBM samples. The chemokine receptor profile of the IM indicated the predominance of Thl mediated immune responses in all three IM. Our studies identified three ligand-receptor pairs, namely CXCL10/CXCR3, CXCL12/CXCR4, and CCL2/CCR2, as potential targets for chemokine-based therapy in IM.},
  author       = {De Paepe, Boel and Creus, Kim and De Bleecker, Jan},
  issn         = {0077-8923},
  journal      = {Annals of the New York Academy of Sciences},
  language     = {eng},
  pages        = {441--453},
  title        = {Chemokine profile of different inflammatory myopathies reflects humoral versus cytotoxic immune responses},
  url          = {http://dx.doi.org/10.1196/annals.1398.050},
  volume       = {1109},
  year         = {2007},
}

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