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Cytokine secretion by CD4+ T cells at the immunological synapse requires Cdc42-dependent local actin remodeling but not microtubule organizing center polarity.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Sep 01; Vol. 189 (5), pp. 2159-68. Date of Electronic Publication: 2012 Jul 20. - Publication Year :
- 2012
-
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.
- Subjects :
- Actins antagonists & inhibitors
Actins deficiency
CD4-Positive T-Lymphocytes cytology
Cell Line, Transformed
Coculture Techniques
Exocytosis immunology
HEK293 Cells
Humans
Immunological Synapses immunology
Immunological Synapses physiology
Jurkat Cells
Microtubule-Organizing Center immunology
Polymerization
Primary Cell Culture
Actins metabolism
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Cell Polarity immunology
Cytokines metabolism
Immunological Synapses metabolism
Microtubule-Organizing Center metabolism
cdc42 GTP-Binding Protein physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 189
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22821962
- Full Text :
- https://doi.org/10.4049/jimmunol.1200156