The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation

Jun Ichiro Suzuki, Sho Yamasaki, Jennifer Wu, Gary A. Koretzky, Takashi Saito

    Research output: Contribution to journalArticle

    83 Citations (Scopus)

    Abstract

    The dynamic rearrangement of the actin cytoskeleton plays critical roles in T-cell receptor (TCR) signaling and immunological synapse (IS) formation in T cells. Following actin rearrangement in T cells upon TCR stimulation, we found a unique ring-shaped reorganization of actin called the "actin cloud," which was specifically induced by outside-in signals through lymphocyte function-associated antigen-1 (LFA-1) engagement. In T-cell-antigen-presenting cell (APC) interactions, the actin cloud is generated in the absence of antigen and localized at the center of the T-cell-APC interface, where it accumulates LFA-1 and tyrosine-phosphorylated proteins. The LFA-1-induced actin cloud formation involves ADAP (adhesion- and degranulation-promoting adaptor protein) phosphorylation, LFA-1/ADAP assembly, and c-Jun N-terminal kinase (JNK) activation, and occurs independent of TCR and its proximal signaling. The formation of the actin cloud lowers the threshold for subsequent T-cell activation. Thus, the actin cloud induced by LFA-1 engagement may serve as a possible platform for LFA-1-mediated costimulatory function for T-cell activation.

    Original languageEnglish
    Pages (from-to)168-175
    Number of pages8
    JournalBlood
    Volume109
    Issue number1
    DOIs
    Publication statusPublished - Jan 1 2007

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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