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Dendritic Cells in the Pathogenesis of Sarcoidosis

¹ Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York; and ² Department of Dermatology, New York University School of Medicine, New York, New York

Correspondence and requests for reprints should be addressed to Lisa C. Zaba, M.D., Ph.D., Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10065. E-mail: lzaba{at}rockefeller.edu

Sarcoidosis is a noncaseating granulomatous disease, likely of autoimmune etiology, that causes inflammation and tissue damage in multiple organs, most commonly the lung, but also skin, and lymph nodes. Reduced dendritic cell (DC) function in sarcoidosis peripheral blood compared with peripheral blood from control subjects suggests that blunted end organ cellular immunity may contribute to sarcoidosis pathogenesis. Successful treatment of sarcoidosis with tumor necrosis factor (TNF) inhibitors, which modulate DC maturation and migration, has also been reported. Together, these observations suggest that DCs may be important mediators of sarcoidosis immunology. This review focuses on the phenotype and function of DCs in the lung, skin, blood, and lymph node of patients with sarcoidosis. We conclude that DCs in end organs are phenotypically and functionally immature (anergic), while DCs in the lymph node are mature and polarize pathogenic Th1 T cells. The success of TNF inhibitors is thus likely secondary to inhibition of DC-mediated Th1 polarization in the lymph node.

Key Words: sarcoidosis • granuloma • dendritic cell • macrophage • inflammation

CLINICAL RELEVANCE This review focuses on dendritic cells as integral players in sarcoidosis pathogenesis. As such, these cells become potential therapeutic targets.