Dermal Dendritic Cells, and not Langerhans Cells, Play an Essential Role in Inducing an Immune Response 1

• Published in: The Journal of immunology (1950) Vol. 180; no. 5; pp. 3057 - 3064
• Main Authors: Fukunaga, Atsushi, Khaskhely, Noor M., Sreevidya, Coimbatore S., Byrne, Scott N., Ullrich, Stephen E.
• Format: Journal Article
• Language: English
• Published: 01.03.2008
• ISSN: 0022-1767; 1550-6606

Langerhans cells (LCs) serve as epidermal sentinels of the adaptive immune system. Conventional wisdom suggests that LC encounter antigen in the skin, and then migrate to the draining lymph nodes, where the antigen is presented to T cells thus initiating an immune response. Platelet-activation factor (PAF) is a phospholipid mediator with potent biological effects. During inflammation, PAF mediates recruitment of leukocytes to inflammatory sites. Here we tested a hypothesis that PAF induces LC migration. Applying 2,4-dinitrofluorobenzene (DNFB) to wild-type (WT) mice activated LC migration. In contrast, applying DNFB to PAF receptor (PAFR)-deficient mice or mice injected with PAF receptor antagonists failed to induce LC migration. Moreover, after FITC application the appearance of hapten-laden LCs (FITC + , CD11c + , Langerin + ) in the lymph nodes of PAF receptor deficient mice was significantly depressed compared with that found in WT mice. LC chimerism indicates that PAF receptor on keratinocytes but not LCs is responsible for LC migration. Contrary to the diminution of LC migration in PAF receptor-deficient mice, we did not observe any difference in the migration of hapten-laden dDCs (FITC + , CD11c + , Langerin − ) into the lymph nodes of PAF receptor-deficient mice. In addition, the contact hypersensitivity response generated in WT or PAF receptor-deficient mice was identical. Finally, dDCs, but not LCs isolated from the draining lymph nodes after hapten application activated T cell proliferation. These findings suggest that LC migration may not be responsible for the generation of CHS, and dDCs may play a more important role.