HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization.
We investigated the role of acetylated microtubules in the antigen-specific interaction of T helper and antigen-presenting cells (APCs). In T cells, acetylated microtubules concentrated at contact site with APCs, surrounding clusters of CD3 and LFA-1. TcR engagement induced a transient deacetylation of microtubules at early times and an enhanced acetylation at late times. Confocal videomicroscopy studies revealed that the HDAC6 tubulin deacetylase was translocated and concentrated at the contact site of T cells with APCs. Overexpression of HDAC6 but not a dead deacetylase mutant in T cells disorganized CD3 and LFA-1 at the immune synapse. This effect was reverted by treatment with the deacetylase inhibitor trichostatin A. The antigen-specific translocation of the microtubule organizing center (MTOC) and IL-2 production were also severely impaired by overexpression of HDAC6. Our results underscore the key role for HDAC6 in the organization of the immune synapse and the antigen-specific reorientation of the MTOC.
Serrador
Juan M
JM
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, E-28006 Madrid, Spain.
Cabrero
Jose Román
JR
Sancho
David
D
Mittelbrunn
María
M
Urzainqui
Ana
A
Sánchez-Madrid
Francisco
F
D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D022101:Microtubule-Organizing Center / Q000276:immunology / Q000378:metabolism; D008870:Microtubules / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D014404:Tubulin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D014404:Tubulin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases