Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine expression in rheumatoid synovium.
It remains to be clarified whether dendritic cells (DC) reach the rheumatoid arthritis (RA) synovium, considered an ectopic lymphoid organ, as mature cells or undergo local maturation. We characterized by immunohistochemistry the DC subsets and used tonsils as a control. Immature and mature DC were defined by CD1a and DC-lysosome-associated membrane protein/CD83 expression, respectively. Immature DC were mainly detected in the lining layer in RA synovium. Mature DC were exclusively detected in the lymphocytic infiltrates. The DC-lysosome-associated membrane protein/CD1a ratio was 1.1 in RA synovium and 5.3 in tonsils, suggesting the relative accumulation of immature DC in RA synovium. We then focused on the expression of CCL20/CCR6 and CCL19/CCR7, CCL21/CCR7 chemokine/receptor complex, which control immature and mature DC migration respectively. A close association was observed between CCL20-producing cells and CD1a(+) cells, suggesting the contribution of CCL20 to CCR6(+) cell homing. Conversely, CCL21 and CCL19 expression was only detected in perivascular infiltrates. The association among CCL19/21-producing cells, CCR7 expression, and mature DC accumulation is in line with the roles of these chemokines in mature CCR7(+) DC homing to lymphocytic infiltrates. The role of DC in disease initiation and perpetuation makes chemokines involved in DC migration a potential therapeutic target.
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Guillaume
G
Department of Immunology and Rheumatology and Institut National de la Sante et de la Recherche Médicale Unité 403, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France.
Lebecque
Serge
S
Miossec
Pierre
P
D015703:Antigens, CD; D018949:Antigens, CD1 / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D019013:CD40 Antigens / Q000096:biosynthesis; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D018925:Chemokines / Q000096:biosynthesis*; D019742:Chemokines, CC / Q000096:biosynthesis; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013583:Synovial Membrane / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018949:Antigens, CD1; D015415:Biomarkers; D019013:CD40 Antigens; D015816:Cell Adhesion Molecules, Neuronal; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D016167:Integrin alphaXbeta2; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D000097802:CD83 Antigen; C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human; C419393:CD1a antigen; C095362:limbic system-associated membrane protein