The Journal of Experimental Medicine
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Published 19 August 2002. doi:10.1084/jem.20020018
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© Rockefeller University Press, 0022-1007/2002/8/417/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 4, August 19, 2002 417-430

Accumulation of Immature Langerhans Cells in Human Lymph Nodes Draining Chronically Inflamed Skin

F. Geissmann1, M.C. Dieu-Nosjean2, C. Dezutter3, J. Valladeau4, S. Kayal1, M. Leborgne1, N. Brousse1, S. Saeland4 and J. Davoust2

1 IFR Necker-Enfants Malades, 75015 Paris, France
2 U255 INSERM, 75005 Paris, France
3 U346 INSERM, 69437 Lyon, France
4 Schering Plough Laboratory for Immunological Research, 69571 Dardilly, France

Address correspondence to F. Geissmann, Service d'Anatomie Pathologique, Hopital Necker-Enfants Malades. Phone: 33-1-44-49-06-75; Fax: 33-1-44-49-06-76; E-mail: geissman{at}necker.fr or geissman{at}saturn.med.nyu.edu

The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207+ LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC–lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-ß1, we further found that tumor necrosis factor (TNF)-{alpha}, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC–LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation.

Key Words: Langerhans cells • dendritic cells • inflammation • cell differentiation • migration


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