Moalli, Federica; Ficht, Xenia; Germann, Philipp; Vladymyrov, Mykhailo; Stolp, Bettina; de Vries, Ingrid; Lyck, Ruth; Balmer, Jasmin Maria; Fiocchi, Amleto; Kreutzfeldt, Mario; Merkler, Doron; Iannacone, Matteo; Ariga, Akitaka; Stoffel, Michael Hubert; Sharpe, James; Bähler, Martin; Sixt, Michael; Diz-Muñoz, Alba; Stein, Jens Volker (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8 T cells. Journal of experimental medicine, 215(7), pp. 1869-1890. Rockefeller University Press 10.1084/jem.20170896
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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.
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