Abstract
CCR7 and its ligands CCL19 and CCL21 are a key chemokine system in T cell priming
in secondary lymphoid organs, and are rarely expressed in normal muscle tissue. We
immunohistochemically investigated the expression of this chemokine system in the
muscles of seven patients with inclusion body myositis (IBM). In all cases, CCR7+
mononuclear cells infiltrated in the endomysium, preferentially surrounded and invaded
nonnecrotic muscle fibers. Double immunostaining revealed that such CCR7+ mononuclear
cells included BDCA-1+ myeloid dendritic cells as well as CD8+ cells, CD4+ cells and
CD68+ macrophages. On the other hand, CCL19 was widely expressed on muscle fibers
including those invaded by mononuclear cells. CCL19 was also expressed diffusely on
endomysial mononuclear cells and endothelium of vessels. Immunoreactivities of CCL21
were detected on some muscle fibers and mononuclear cells. By RT-PCR analyses, mRNA
of CCR7 was detected in all the patients and that of CCL19 and CCL21 was detected
in six. These findings showed that the CCL19, CCL21/CCR7 chemokine system is expressed
in muscles of IBM. The chemokine mediated attraction in dendritic and other immune
cells and muscle cells may be crucial in sustained antigen presentation, T cell activation
and immune attack to muscles in the pathogenesis of IBM.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches.Lancet Neurol. 2007; 6: 620-631
- Sporadic inclusion body myositis-diagnosis, pathogenesis and therapeutic strategies.Nat Clin Pract Neurol. 2006; 2: 437-447
- Inclusion body myositis: clonal expansions of muscle-infiltrating T cells persists over time.Scand J Immunol. 2003; 58: 195-200
- Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time. Studies in repeated muscle biopsies.Brain. 2000; 123: 2030-2039
- T-cell heterogeneity in muscle lesions of inclusion body myositis.J Neuroimmunol. 1998; 84: 86-91
- Sporadic inclusion body myositis: counts of different types of abnormal fibers.Ann Neurol. 1996; 39: 139-143
- Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues.Mol Immunol. 2005; 42: 799-809
- Chemokines determine local lymphoneogenesis and a reduction of circulating CXCR4+ T and CCR7 B and T lymphocytes in thyroid autoimmune diseases.J Immunol. 2003; 170: 6320-6328
- Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine mediated retention mechanism.Gut. 2006; 55: 220-227
- Endothelial induction of the T-cell chemokine CCL21 in T-cell autoimmune diseases.Blood. 2003; 101: 801-806
- Focal interstitial CC chemokine receptor 7 (CCR7) expression in idiopathic interstitial pneumonia.J Clin Pathol. 2006; 59: 28-39
- Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis.Am J Pathol. 2002; 161: 1815-1823
- Expression of CCR7 and its ligands CCL19/CCL21 in muscles of polymyositis.J Neurol Sci. 2006; 249: 158-165
- Epstein–Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors.J virol. 1993; 67: 2209-2220
- Molecular cloning of a novel human CC chemokine secondary lymphoid-tissue chemokine that is a potent chemoattractant for lymphocytes and mapped to chromosome 9p13.J Biol Chem. 1997; 272: 19518-19524
- Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a specific functional ligand for EBI1, CCR7.J Biol Chem. 1997; 272: 13803-13809
- Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis. Interaction with chemokines and Th1 cytokine-producing cells.Arthritis Rheum. 2004; 50: 199-208
- Chemokine receptor CCR7 is expressed in muscle fibers in juvenile dermatomyositis.Biochem Biophys Res Commun. 2005; 333: 540-543
- Characterization of human blood dendritic cell subsets.Blood. 2002; 100: 4512-4520
- Dendritic cells: immune regulators in health and disease.Physiol Rev. 2002; 82: 97-130
- Myeloid dendritic cells in inclusion-body myositis and polymyositis.Muscle Nerve. 2007; 35: 17-23
- Distinct effect of CD40 and TNF-signaling on the chemokine/chemokine receptor expression and function of the human monocyte-derived dendritic cells.Cell Mol Immunol. 2008; 5: 121-131
- Costimulatory markers in muscle of patients with idiopathic inflammatory myopathies and in cultured muscle cells.Clin Immunol. 1999; 92: 161-169
- Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40–CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production.J Immunol. 2000; 164: 6593-6600
- Distinct patterns and kinetics of chemokine production regulate dendritic cell function.Eur J Immunol. 1999; 29: 1617-1625
- Immunocytochemical study of CD45 T cell isoforms in inflammatory myopathies.Am J Pathol. 1995; 146: 1178-1187
- The multiple personalities of the chemokine receptor CCR7 in dendritic cells.J Immunol. 2006; 176: 5153-5159
- CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities.Blood. 2003; 101: 4923-4929
- CCL19 induces rapid dendritic extension of murine dendritic cells.Blood. 2002; 100: 1948-1956
- CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells.Immunity. 2005; 22: 493-505
- Chemokine receptor CCR7 induces intracellular signaling that inhibits apoptosis of mature dendritic cells.Blood. 2004; 104: 619-625
- Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position.Nature. 2002; 416: 94-99
- Dendritic cell-independent B cell activation during acute virus infection: a role for early CCR7-driven B-T helper cell collaboration.J Immunol. 2007; 178: 1468-1476
- Plasma cells in muscle in inclusion body myositis and polymyositis.Neurology. 2005; 65: 1782-1787
- Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM.Neurology. 2008; 70: 418-424
Article info
Publication history
Published online: January 27, 2009
Accepted:
December 17,
2008
Received in revised form:
December 12,
2008
Received:
June 16,
2008
Identification
Copyright
© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
