Dendritic cells regulate T-cell deattachment through the integrin-interacting protein CYTIP.
When T cells are primed by dendritic cells (DCs) to initiate antigen-specific immune responses screening for matching antigen receptor-MHC/peptide pairs takes place in DC-T-cell conjugates. For an immune response DC-T-cell conjugates formed during priming events need to dissolve. Although detailed knowledge on molecules involved in the conjugate formation is available, dissolving of them has not been considered to be an active process. Here, we identify CYTIP (cytohesin-interacting protein) to mediate DC-T-cell deattachment. CYTIP, which is induced during maturation of DCs, shortly accumulates to the contact zones with T cells within the first hour of coculture. Specific silencing of CYTIP results in stronger adhesion of DCs to T cells and to fibronectin. When a need for deattachment is created in a T-cell priming assay by only partially loading DCs with antigen, CYTIP silencing causes reduced priming capacity. Thus, CYTIP allows DCs to actively control DC-T-cell interactions.
Hofer
Susanne
S
Department of Dermatology, Medical University of Innsbruck, Innsbruck, Austria.
Pfeil
Karina
K
Niederegger
Harald
H
Ebner
Susanne
S
Nguyen
Van Anh
VA
Kremmer
Elisabeth
E
Auffinger
Margit
M
Neyer
Susanne
S
Fürhapter
Christina
C
Heufler
Christine
C
D017951:Antigen Presentation / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005353:Fibronectins / Q000276:immunology; D020868:Gene Silencing / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors
C084539:CYTIP protein, human; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D014157:Transcription Factors