Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN-α.
Migration of DC into lymphatic vessels ferries antigenic cargo and pro-inflammatory stimuli into the draining LN. Given that tissues under the influence of viral infections produce type I IFN, it is conceivable that these cytokines enhance DC migration in order to facilitate an antiviral immune response. Cultured lymphatic endothelium monolayers pretreated with TNF-α were used to model this phenomenon under inflammatory conditions. DC differentiated in the presence of either IFN-α2b or IFN-α5 showed enhanced adhesion to cultured lymphatic endothelial cells. These pro-adhesive effects were mediated by DC, not the lymphatic endothelium, and correlated with increased DC transmigration across lymphatic endothelial cell monolayers. Transmigration was guided by chemokines acting on DC, and blocking experiments with mAb indicated a role for LFA-1. Furthermore, incubation of DC with IFN-α led to the appearance of active conformation epitopes on the CD11a integrin chains expressed by DC. Differentiation of mouse DC in the presence of IFN-α also increased DC migration from inflammed footpads toward popliteal LN. Collectively, these results indicate a role for type I IFN in directing DC toward LN under inflammatory conditions.
Center for Applied Medical Research, School of Medicine, University of Navarra, Pamplona, Spain. arouzaut@unav.es
Ana
A
Rouzaut
Saray
S
Garasa
Alvaro
A
Teijeira
Iranzu
I
González
Ivan
I
Martinez-Forero
Natalia
N
Suarez
Esther
E
Larrea
Carlos
C
Alfaro
Asís
A
Palazón
Juan
J
Dubrot
Sandra
S
Hervás-Stubbs
Ignacio
I
Melero
D000818:Animals; D040881:CD11a Antigen / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D004729:Endothelium, Lymphatic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D040881:CD11a Antigen; D016898:Interferon-alpha; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha