title: CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells.
abstract: 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 (S1P(1)) by CD69-/- DCs, whereas S1P(3) 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 S1P(1) 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.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Lamana
authors.forename: Pilar
authors.initials: P
authors.lastname: Martin
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.forename: Laura
authors.initials: L
authors.lastname: Martinez-Muñoz
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Cruz-Adalia
authors.forename: Marta
authors.initials: M
authors.lastname: Ramirez-Huesca
authors.forename: Cristina
authors.initials: C
authors.lastname: Escribano
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gollmer
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rodriguez-Fernandez
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanchez-Madrid
authors.forename: Gloria Martinez
authors.initials: GM
authors.lastname: del Hoyo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D007801:Langerhans Cells / Q000166:cytology / Q000502:physiology*; D037181:Lectins, C-Type / Q000032:analysis / Q000502:physiology*; D008246:Lysophospholipids / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D008246:Lysophospholipids; D013110:Sphingosine; D000099192:CD69 Antigens; C060506:sphingosine 1-phosphate