Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis: Interaction with chemokines and Th1 cytokine-producing cells.
OBJECTIVE
To clarify the involvement of dendritic cells (DCs), chemokines, and proinflammatory Th1 cytokines in the pathogenesis of the chronic muscle diseases dermatomyositis (DM) and polymyositis (PM).


METHODS
We characterized by immunohistochemistry the DC subsets and their interaction with cells producing chemokines and the Th1 cytokines interleukin-17 (IL-17) and interferon-gamma (IFNgamma). Immature and mature DCs were defined by the expression of CD1a and DC-LAMP/CD83, respectively.


RESULTS
Immature DCs were mainly detected in lymphocytic infiltrates in DM and PM muscle tissue samples. Mature DCs were detected in perivascular infiltrates and surrounded muscle fibers. IL-17-positive and IFNgamma-positive cells were also observed in perivascular infiltrates in both cases. We then focused on the expression of the CCL20/CCR6 chemokine/receptor complex, which controls immature DC migration, and on the expression of the CCL19/CCR7 and CCL21/CCR7 chemokine/receptor complexes, which control mature DC migration. CCL20 and CCR6 colocalized in lymphocytic infiltrates in DM and PM samples. CCL21 was rarely observed in DM samples and never observed in PM samples. CCL19- and CCR7-expressing cells were absent in both tissues.


CONCLUSIONS
The close association between CCL20/CCR6 and immature DCs suggests the contribution of CCL20 to CCR6+ immature DC homing. Detection of mature DCs in DM and PM muscle tissue samples despite the lack of CCL19 and CCR7 is evidence for a local maturation of DCs in inflammatory muscle tissue without lymphoid organ organization.
Page
Guillaume
G
INSERM U403, Hôpital Edouard Herriot, Lyon, France.
Chevrel
Guillaume
G
Miossec
Pierre
P
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000276:immunology; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003882:Dermatomyositis / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology; D017285:Polymyositis / Q000276:immunology* / Q000473:pathology*; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism
C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D019742:Chemokines, CC; D020381:Interleukin-17; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D007371:Interferon-gamma