Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain.
Dendritic cells (DCs) sample peripheral tissues of the body in search of antigens to present to T cells. This requires two processes, antigen processing and cell motility, originally thought to occur independently. We found that the major histocompatibility complex II-associated invariant chain (Ii or CD74), a known regulator of antigen processing, negatively regulates DC motility in vivo. By using microfabricated channels to mimic the confined environment of peripheral tissues, we found that wild-type DCs alternate between high and low motility, whereas Ii-deficient cells moved in a faster and more uniform manner. The regulation of cell motility by Ii depended on the actin-based motor protein myosin II. Coupling antigen processing and cell motility may enable DCs to more efficiently detect and process antigens within a defined space.
Faure-André
Gabrielle
G
INSERM U653, Institut Curie, 12 rue Lhomond, 75005, Paris, France.
Vargas
Pablo
P
Yuseff
Maria-Isabel
MI
Heuzé
Mélina
M
Diaz
Jheimmy
J
Lankar
Danielle
D
Steri
Veronica
V
Manry
Jeremy
J
Hugues
Stéphanie
S
Vascotto
Fulvia
F
Boulanger
Jérôme
J
Raposo
Graça
G
Bono
Maria-Rosa
MR
Rosemblatt
Mario
M
Piel
Matthieu
M
Lennon-Duménil
Ana-Maria
AM
D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024462:Myosin Type II / Q000378:metabolism*; D010766:Phosphorylation
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; C045084:invariant chain; D002403:Cathepsins; C028217:cathepsin S; D024462:Myosin Type II