title: Cytokine secretion by CD4+ T cells at the immunological synapse requires Cdc42-dependent local actin remodeling but not microtubule organizing center polarity.
abstract: Cytokine secretion by T lymphocytes plays a central role in mounting adaptive immune responses. However, little is known about how newly synthesized cytokines, once produced, are routed within T cells and about the mechanisms involved in regulating their secretions. In this study, we investigated the role of cytoskeleton remodeling at the immunological synapse (IS) in cytokine secretion. We show that a key regulator of cytoskeleton remodeling, the Rho GTPase Cdc42, controls IFN-γ secretion by primary human CD4+ T lymphocytes. Surprisingly, microtubule organizing center polarity at the IS, which does not depend on Cdc42, is not required for cytokine secretion by T lymphocytes, whereas microtubule polymerization is required. In contrast, actin remodeling at the IS, which depends on Cdc42, controls the formation of the polymerized actin ring at the IS, the dynamic concentration of IFN-γ-containing vesicles inside this ring, and the secretion of these vesicles. These results reveal a previously unidentified role of Cdc42-dependent actin remodeling in cytokine exocytosis at the IS.
authors: Institut Curie, Centre de Recherche, Paris F-75248, France.
authors: Karine
authors: K
authors: Chemin
authors: Armelle
authors: A
authors: Bohineust
authors: Stéphanie
authors: S
authors: Dogniaux
authors: Marie
authors: M
authors: Tourret
authors: Sarah
authors: S
authors: Guégan
authors: Francesc
authors: F
authors: Miro
authors: Claire
authors: C
authors: Hivroz
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002461:Cell Line, Transformed; D016764:Cell Polarity / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D005089:Exocytosis / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D019169:Jurkat Cells; D022101:Microtubule-Organizing Center / Q000276:immunology / Q000378:metabolism*; D058105:Polymerization; D061251:Primary Cell Culture; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*
chemical_list: D000199:Actins; D016207:Cytokines; D020764:cdc42 GTP-Binding Protein