TY - JOUR AB - 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. AU - Moalli, Federica AU - Ficht, Xenia AU - Germann, Philipp AU - Vladymyrov, Mykhailo AU - Stolp, Bettina AU - de Vries, Ingrid AU - Lyck, Ruth AU - Balmer, Jasmin AU - Fiocchi, Amleto AU - Kreutzfeldt, Mario AU - Merkler, Doron AU - Iannacone, Matteo AU - Ariga, Akitaka AU - Stoffel, Michael H. AU - Sharpe, James AU - Bähler, Martin AU - Sixt, Michael K AU - Diz-Muñoz, Alba AU - Stein, Jens V. ID - 6497 IS - 7 JF - The Journal of Experimental Medicine SN - 0022-1007 TI - The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells VL - 2015 ER -