Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis
Consuelo M. López de Padilla
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorAbbe N. Vallejo
Children's Hospital of Pittsburgh, the Cancer Institute, and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Search for more papers by this authorKelly T. McNallan
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorRichard Vehe
University of Minnesota Medical School, Minneapolis
Search for more papers by this authorStephen A. Smith
Hennepin County Medical Center, Minneapolis, Minnesota
Search for more papers by this authorAllan B. Dietz
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorStanimir Vuk-Pavlovic
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorCorresponding Author
Ann M. Reed
Mayo Clinic College of Medicine, Rochester, Minnesota
Mayo Clinic, Division of Rheumatology, E15, Departments of Medicine and Pediatrics, 200 First Street SW, Rochester, MN 55905Search for more papers by this authorConsuelo M. López de Padilla
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorAbbe N. Vallejo
Children's Hospital of Pittsburgh, the Cancer Institute, and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Search for more papers by this authorKelly T. McNallan
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorRichard Vehe
University of Minnesota Medical School, Minneapolis
Search for more papers by this authorStephen A. Smith
Hennepin County Medical Center, Minneapolis, Minnesota
Search for more papers by this authorAllan B. Dietz
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorStanimir Vuk-Pavlovic
Mayo Clinic College of Medicine, Rochester, Minnesota
Search for more papers by this authorCorresponding Author
Ann M. Reed
Mayo Clinic College of Medicine, Rochester, Minnesota
Mayo Clinic, Division of Rheumatology, E15, Departments of Medicine and Pediatrics, 200 First Street SW, Rochester, MN 55905Search for more papers by this authorAbstract
Objective
To examine whether dendritic cells (DCs) are constituents of muscle inflammation in juvenile dermatomyositis (DM).
Methods
The types, numbers, and activation state of DC subsets in inflamed muscle tissue from patients with juvenile DM and in noninflamed muscle tissue from control subjects were examined by multicolor immunofluorescence. Chemokine expression of the muscle-infiltrating cells was examined by laser capture microdissection and quantitative polymerase chain reaction.
Results
Plasmacytoid DCs were the predominant component of the inflamed muscle tissue from patients with juvenile DM. These cells were identified by coexpression of CD4 and CD123, but not CD11c, and also expressed CD83, indicating maturity of the cells. In contrast, in noninflamed muscle, plasmacytoid DCs were scarce and did not express CD83. Mononuclear cells surrounding the blood vessels of inflamed muscle contained abundant transcripts of CCL19 and CCL21, but very little CCL18 transcripts. In contrast, cells from noninflamed muscle contained negligible amounts of CCL19 and CCL21, but had high amounts of CCL18. Both the inflamed and noninflamed muscle tissue had equivalent levels of CXCL12 transcripts, but inflamed muscle contained more transcripts of the CXCL12 receptor CXCR4.
Conclusion
These findings are consistent with the idea that plasmacytoid DCs are mediators of muscle inflammation in juvenile DM. The abundance of CD83+ plasmacytoid DCs in perivascular areas and the overexpression of CCL19 and CCL21 in perivascular cellular foci suggest that in situ activation and maturation of resident plasmacytoid DCs are central to the initiation and perpetuation of muscle inflammation in juvenile DM.
REFERENCES
- 1 Pachman LM. Juvenile dermatomyositis: immunogenetics, pathophysiology, and disease expression. Rheum Dis Clin North Am 2002; 28: 579–602.
- 2 Pachman LM, Hayford JR, Hochberg MC, Pallansch MA, Chung A, Daugherty CD, et al. New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis. Arthritis Rheum 1997; 40: 1526–33.
- 3 De Visser MA, Emslie-Smith M, Engel AG. Early ultrastructural alterations in adult dermatomyositis: capillary abnormalities precede other structural changes in muscle. J Neurol Sci 1989; 94: 181–92.
- 4 Dalakas MC. Immunopathogenesis of inflammatory myopathies. Ann Neurol 1995; 37 Suppl 1: S74–86.
- 5 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245–52.
- 6 Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767–811.
- 7 Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21: 685–711.
- 8 Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A 2002; 99: 351–8.
- 9 Cravens PD, Lipsky PE. Dendritic cells, chemokine receptors and autoimmune inflammatory diseases. Immunol Cell Biol 2002; 80: 497–505.
- 10 Drakesmith H, Chain B, Beverley P. How can dendritic cells cause autoimmune diseases? Immunol Today 2000; 21: 214–7.
- 11 Colonna M, Trinchieri G, Liu Yong-Jun. Plasmacytoid dendritic cells in immunity. Nat Immunol 2004; 5: 1219–26.
- 12 Jahnsen FL, Farkas L, Lund-Johansen F, Brandtzaeg P. Involvement of plasmacytoid dendritic cells in human diseases. Hum Immunol 2002; 63: 1201–5.
- 13 Van Krinks CH, Matyszak MK, Hill Gaston JS. Characterization of plasmacytoid dendritic cells in the inflammatory arthritis synovial fluid. Rheumatology (Oxford) 2004; 43: 453–60.
- 14 Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon-α/β-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol 2001; 159: 237–43.
- 15 Cavanagh LL, Boyce A, Smith L, Padmanabha J, Filguiera L, Pietschmann P, et al. Rheumatoid arthritis synovium contains plasmacytoid dendritic cells. Arthritis Res Ther 2005; 7: R230–40.
- 16 Facchetti F, Vermi W, Mason D, Colonna M. The plasmacytoid monocyte/interferon producing cells. Virchows Arch 2003; 443: 703–17.
- 17 Cella M, Jarrosay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 1999; 5: 919–23.
- 18 Vallin H, Blomberg S, Alm GV, Cederblad B, Ronnblom L. Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-α (IFN-α) production acting on leukocytes resembling immature dendritic cells. Clin Exp Immunol 1999; 115: 196–202.
- 19 Tezak Z, Hoffman EP, Lutz JL, Fedczyna TO, Stephan D, Bremer EG, et al. Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis. J Immunol 2002; 168: 4154–63.
- 20 Page G, Chevred G, Miossec P. 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.
- 21 Pedrol E, Grau JM, Casademont J, Cid MC, Masanes F, Fernandez-Sola J, et al. Idiopathic inflammatory myopathies: immunohistochemical analysis of the major histocompatibility complex antigen expression, inflammatory infiltrate phenotype and activation cell markers. Clin Neuropathol 1995; 14: 179–84.
- 22 Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975; 292: 344–7.
- 23 Testa U. IL3RA (interleukin-3 receptor α). Atlas Genet Cytogenet Oncol Haematol May 2005. URL: //http://atlasgeneticsoncology.org/Genes/IL3RAID40959chXp22Yp13.pdf.
- 24 Dietz AB, Bulur PA, Erickson MR, Wettstein PJ, Litzow MR, Wyatt WA, et al. Optimizing preparation of normal dendritic cells and bcr-abl+ mature dendritic cells derived from immunomagnetically purified CD14+ cells. J Hematother Stem Cell Res 2000; 9: 95–101.
- 25 Summers KL, Hock BD, McKenzie JL, Hart DN. Phenotypic characterization of five dendritic cell subsets in human tonsils. Am J Pathol 2001; 159: 285–95.
- 26 Mahnke K, Enk AH. Dendritic cells: key cells for the induction of regulatory T cells? Curr Top Microbiol Immunol 2005; 293: 133–50.
- 27 Lechmann M, Berchtold S, Hauber J, Steinkasserer A. CD83 on dendritic cells: more than just a marker for maturation. Trends Immunol 2002; 23: 273–5.
- 28 Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001; 410: 50–6.
- 29 Zeelenberg IS, Ruuls-Van Stalle L, Roos E. The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Res 2003; 63: 3833–9.
- 30 Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, et al. The nature of the principal type 1 interferon producing cells in human blood. Science 1999; 289: 1835–7.
- 31 Ronnblom L, Gunnar VA. A pivotal role for the natural interferon α-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J Exp Med 2001; 194: F59–63.
- 32 Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, Tawil R, et al. Interferon α/β-mediated innate immune mechanism in dermatomyositis. Ann Neurol 2005; 57: 664–78.
- 33 Palucka KA. Blanck JP, Bennett L, Pascual V, Banchereau J. Cross-regulation of TNF and IFN-α in autoimmune diseases. Proc Natl Acad Sci U S A 2005; 102: 3372–7.
- 34 Grouard G, Rissoan MC, Filguiera L, Durand I, Banchereau J, Liu YJ, et al. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J Exp Med 1997; 185: 1101–11.
- 35 Arahata K, Engel A. Monoclonal antibody analysis of mononuclear cells in myopathies. I. Quantification of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 1984; 16: 193–208.
- 36 Lundberg IE. The physiology of inflammatory myopathies: an overview. Acta Physiol Scand 2001; 171: 207–13.
- 37 Page G, Lebecque S, Miossec P. Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine expression in rheumatoid synovium. J Immunol 2002; 168: 5333–41.
- 38 Sozzani S, Allavena P, Vecchi A, Mantovani A. The role of chemokines in the regulation of dendritic cell trafficking. J Leukoc Biol 1999; 66: 1–9.
- 39 Vulcano M, Struyf S, Scapini P, Cassatella M, Bernasconi S, Bonecchi R, et al. Unique regulation of CCL18 production by maturing dendritic cells. J Immunol 2003; 170: 3843–9.
- 40 Vissers JL, Hartgers FC, Lindhout E, Teunissen MB, Figdor CG, Adema GJ, et al. Quantitative analysis of chemokine expression by dendritic cell subsets in vitro and in vivo. J Leukoc Biol 2001; 69: 785–93.
- 41 Hjelmstrom P. Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines. J Leukoc Biol 2001; 69: 331–9.
- 42 Weyand CM, Kang YM, Kurtin PJ, Goronzy JJ. The power of the third dimension: tissue architecture and autoimmunity in rheumatoid arthritis. Curr Opin Rheumatol 2003; 15: 259–66.
- 43 De Bleecker JL, Engel AG, Butcher EC. Peripheral lymphoid tissue-like adhesion molecule expression in nodular infiltrates in inflammatory myopathies. Neuromusc Disord 1996; 6: 255–60.
- 44 Facchetti F, De Wolf-Peeters C, van den Oord JJ, De vos R, Desmet VJ. Plasmacytoid T cells: a cell population normally present in the reactive lymph node. An immunohistochemical and electron microscopy study. Hum Pathol 1988; 19: 1085–92.
- 45 Vanbervliet B, Bendriss-Vermare N, Massacrier C, Homey B, de Bouteiller O, Briere F, et al. The inducible CXCR3 ligands control plasmacytoid dendritic cells responsiveness to the constitutive chemokine stromal cell-derived factor 1(SDF-1)/CXCL12. J Exp Med 2003; 198: 823–30.
- 46 Penna G, Sozzani S, Adorini L. Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells. J Immunol 2001; 167: 1862–6.
- 47 Penna G, Vulcano M, Sozzani S, Adorini L. Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells. Hum Immunol 2002; 63: 1164–71.
