Journal Article

CpG motifs induce Langerhans cell migration <i>in vivo</i>

Elisabeth Ban, Loïc Dupré, Emmanuel Hermann, Wolfgang Rohn, Catherine Vendeville, Brigitte Quatannens, Paola Ricciardi-Castagnoli, André Capron and Gilles Riveau

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 12, issue 6, pages 737-745
Published in print June 2000 | ISSN: 0953-8178
Published online June 2000 | e-ISSN: 1460-2377 | DOI: https://dx.doi.org/10.1093/intimm/12.6.737
CpG motifs induce Langerhans cell migration in vivo

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Cytosine–guanosine (CpG) oligonucleotide (CpG-oligo) sequences are immunostimulatory motifs that are present in bacterial DNA and their presence in plasmids might contribute to the immune response generated by DNA vaccination. The cell targets of CpG motifs in vivo have not been characterized yet. In this report we assessed the in vivo effects of CpG motifs on Langerhans cells (LC) migration. We showed that intradermal injection of 10 μg of CpG-containing oligonucleotides in mouse ear induced the local depletion of LC within 2 h of exposure as shown by CD11c and Ia immunohistological staining. To demonstrate that LC depletion was due to LC migration, CpG oligonucleotides were injected into the explants ex vivo, and the CD11c+ cells emigrating from the cultured isolated skin within medium were evaluated by immunostaining and FACS analysis. Our findings demonstrate that CpG motifs induce LC/dendritic cell (DC) migration out of the skin. To assess whether CpG motifs may act directly on LC/DC to induce their emigration we next analyzed the effects of CpG motifs in vitro on the expression of adhesion molecules involved in LC/DC migration. The results of these experiments show that α6 integrins, E-Cadherin, ICAM-1, CD11b and CD11c were differentially regulated upon CpG-oligo treatment of immortalized DC. CpG treatment (10 μg/ml for 8 h) resulted in a 100% increase in ICAM-1 staining intensity, a 50% decrease in E-Cadherin staining and a 25% decrease in α6 integrins staining, while no changes in the levels of CD11b and CD11c expression were recorded. Changes in adhesion molecule expression were mirrored by concomitant changes in the cell morphology that included cell depolarization, the appearance of filopods and loss of adherence. This study provides the first in vivo evidence that CpG motifs signal the migration of LC from the epidermis.

Keywords: adhesion molecules; CpG motifs; DNA vaccine; Langerhans cell; migration; CpG cytosine–guanosine; DC dendritic cell; LC Langerhans cell; TNF tumor necrosis factor

Journal Article.  5945 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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