ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells

Interferon consensus sequence-binding protein (ICSBP) is a transcription factor belonging to the interferon regulatory factor (IRF) family, recently shown to play a critical role in dendritic cell (DC) differentiation. Here, we analyzed the role of ICSBP in the development and trafficking of epiderm...

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Bibliographic Details
Published in:Blood 2004-03, Vol.103 (6), p.2221-2228
Main Authors: Schiavoni, Giovanna, Mattei, Fabrizio, Borghi, Paola, Sestili, Paola, Venditti, Massimo, Morse, Herbert C., Belardelli, Filippo, Gabriele, Lucia
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Communication - immunology
Cell Movement - immunology
Chemotaxis - immunology
Dermatitis - immunology
Dermis - cytology
Dermis - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Interferon Regulatory Factors
Langerhans Cells - cytology
Langerhans Cells - physiology
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Monocytes, macrophages
Myeloid cells: ontogeny, maturation, markers, receptors
Repressor Proteins - genetics
Repressor Proteins - metabolism
T-Lymphocytes - cytology
T-Lymphocytes - immunology
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Summary:Interferon consensus sequence-binding protein (ICSBP) is a transcription factor belonging to the interferon regulatory factor (IRF) family, recently shown to play a critical role in dendritic cell (DC) differentiation. Here, we analyzed the role of ICSBP in the development and trafficking of epidermal Langerhans cells (LCs) and dermal DCs and the implications for initiation of a competent immune response. ICSBP-/- mice exhibited a reduced frequency of LCs and a delayed mobility of DCs from skin that reflected a slower turnover rate in lymph nodes during steady-state conditions. Even under inflammatory changes, ICSBP-/- DCs displayed reduced mobility from skin to lymph nodes and, as a consequence, failed to induce a contact hypersensitivity (CHS) response, suggesting that these DCs were unable to initiate a competent antigen (Ag)–specific T-cell–mediated immunity. Moreover, bone marrow (BM)–derived DCs from ICSBP-/- mice exhibited an immature phenotype and a severe reduction of interleukin 12 (IL-12) expression. These BM DCs also showed a marked defect in their migratory response to macrophage inflammatory protein 3α (MIP-3α), MIP-3β, and the CC chemokine CCL21/6Ckine, which was paralleled by an impaired expression of the CC chemokine receptors, CCR6 and CCR7. Together, these results indicate that ICSBP is critically required for the development and trafficking of skin DCs, thus playing a critical role in the DC-mediated initiation of T-cell immunity.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-09-3007