Actin-bundling protein L-plastin regulates T cell activation

Wang Chen, Sharon Celeste Morley, David Donermeyer, Ivan Peng, Wyne P. Lee, Jason Devoss, Dimitry M. Danilenko, Lin Zhonghua, Zhang Juan, Zhou Jie, Paul M. Allen, Eric J. Brown

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Engagement of TCRs induces actin rearrangements, which are critical for T cell activation. T cell responses require new actin polymerization, but the significance of higher-order actin structures, such as microfilament bundles, is unknown. To determine the role of the actin-bundling protein leukocyte-plastin (L-plastin; LPL) in this process, T cells from LPL-/- mice were studied. LPL-/- T cells were markedly defective in TCR-mediated cytokine production and proliferation. LPL-/- T cells also spread inefficiently on surfaces with immobilized TCR ligands and formed smaller immunological synapses with APCs, likely due to defective formation of lamellipodia. LPL-/- mice showed delayed rejection of skin allografts after release from immunosuppression. Moreover, LPL-/- mice developed much less severe neurologic symptoms in experimental autoimmune encephalomyelitis, which correlated with impaired T cell responses to Ag, manifested by reduced proliferation and production of IFN-g and IL-17. Thus, LPL-dependent actin bundling facilitates the formation of lamellipodia and normal immunological synapses and thereby enables T cell activation.

Original languageEnglish
Pages (from-to)7487-7497
Number of pages11
JournalJournal of Immunology
Volume185
Issue number12
DOIs
StatePublished - Dec 15 2010

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    Chen, W., Morley, S. C., Donermeyer, D., Peng, I., Lee, W. P., Devoss, J., Danilenko, D. M., Zhonghua, L., Juan, Z., Jie, Z., Allen, P. M., & Brown, E. J. (2010). Actin-bundling protein L-plastin regulates T cell activation. Journal of Immunology, 185(12), 7487-7497. https://doi.org/10.4049/jimmunol.1001424