RT Journal Article T1 CD69 Modulates Sphingosine-1-Phosphate-Induced Migration of Skin Dendritic Cells A1 Lamana Domínguez, Amalia A1 Martin, Pilar A1 Fuente, Hortensia de la A1 Martinez-Muñoz, Laura A1 Cruz Adalia, Aranzazu A1 Ramirez-Huesca, Marta A1 Escribano, Cristina A1 Gollmer, Kathrin A1 Mellado, Mario A1 Stein, Jens A1 Rodriguez-Fernandez, Jose Luis A1 Sanchez-Madrid, Francisco A1 Martinez del Hoyo, Gloria AB In this study, we have investigated the role of CD69, an early inducible leukocyte activation receptor, in murine dendritic cell (DC) differentiation, maturation, and migration. Skin DCs and DC subsets present in mouse lymphoid organs express CD69 in response to maturation stimuli. Using a contact sensitization model, we show that skin DCs migrated more efficiently to draining lymph nodes (LNs) in the absence of CD69. This was confirmed by subcutaneous transfer of CD69–/– DCs, which presented an increased migration to peripheral LNs. Two-photon microscopy analysis showed that once DCs reached the LNs, CD69 deficiency did not alter DC interstitial motility in the LNs. Chemotaxis to sphingosine-1-phosphate (S1P) was enhanced in CD69–/– DCs compared with wild-type DCs. Accordingly, we detected a higher expression of S1P receptor type-1 (S1P1) by CD69–/– DCs, whereas S1P3 expression levels were similar in wild-type and CD69–/– DCs. Moreover, in vivo treatment with S1P analogs SEW2871 and FTY720 during skin sensitization reduced skin DC migration to peripheral LNs. These results suggest that CD69 regulates S1P-induced skin DC migration by modulating S1P1 function. Together, our findings increase our knowledge on DC trafficking patterns in the skin, enabling the development of new directed therapies using DCs for antigen (Ag) delivery. PB Elsevier SN 0022-202X YR 2011 FD 2011 LK https://hdl.handle.net/20.500.14352/94309 UL https://hdl.handle.net/20.500.14352/94309 LA eng NO Lamana, Amalia, et al. «CD69 Modulates Sphingosine-1-Phosphate-Induced Migration of Skin Dendritic Cells». Journal of Investigative Dermatology, vol. 131, n.o 7, julio de 2011, pp. 1503-12. https://doi.org/10.1038/jid.2011.54. NO This work was supported by grants MEICA from Genoma España Foundation, SAF 2008-02635 from Ministerio de Ciencia e Innovación, INSINET from Comunidad Autónoma de Madrid, FONCICYT-95395, ALA/127249, and RECAVA RD06/0014-0030 from Instituto de Salud Carlos III to FSM and SAF2008-02719 from Ministerio de Ciencia e Innovación to PM. GMH is supported by Instituto de Salud Carlos III. CNIC is supported by the Spanish Ministry of Health and Consumer Affairs and the Pro-CNIC Foundation. We thank Simon Bartlett for editing the manuscript. NO Ministerio de Ciencia, Innovación y Universidades (España) NO Comunidad de Madrid NO Instituto de Salud Carlos III NO Consejo Nacional de Humanidades, Ciencias y Tecnologías (México) NO Ministerio de Sanidad y Consumo (España) DS Docta Complutense RD 21 abr 2025