The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells

F Moalli, X Ficht, P Germann, M Vladymyrov, B Stolp, I De Vries, R Lyck, J Balmer, A Fiocchi, M Kreutzfeldt, D Merkler, M Iannacone, A Ariga, MH Stoffel, J Sharpe, M Bähler, M Sixt, A Diz‑Muñoz, JV Stein

Research output: Contribution to journalArticle

Abstract

T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/−CD8+T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/−CD8+T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/−CD8+T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations. © 2018 Moalli et al.
Original languageEnglish
Pages (from-to)1869-1890
Number of pages22
JournalJournal of Experimental Medicine
Volume215
Issue number7
DOIs
Publication statusPublished - 2018

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    Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., De Vries, I., Lyck, R., Balmer, J., Fiocchi, A., Kreutzfeldt, M., Merkler, D., Iannacone, M., Ariga, A., Stoffel, MH., Sharpe, J., Bähler, M., Sixt, M., Diz‑Muñoz, A., & Stein, JV. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. Journal of Experimental Medicine, 215(7), 1869-1890. https://doi.org/10.1084/jem.20170896