Anatomic Localization of Immature and Mature Dendritic Cells in an Ectopic Lymphoid Organ: Correlation with Selective Chemokine Expression in Rheumatoid Synovium

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Abstract
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.