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

Moalli, Federica
Ficht, Xenia
Germann, Philipp
Vladymyrov, Mykhailo
Stolp, Bettina
de Vries, Ingrid
Lyck, Ruth
Balmer, Jasmin
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Published in The journal of experimental medicine. 2018, vol. 215, no. 7, p. 1869-1890
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.
PMID: 29875261
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Research group La Sclérose en plaques (908)
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MOALLI, Federica et al. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+ T cells. In: Journal of Experimental Medicine, 2018, vol. 215, n° 7, p. 1869-1890. doi: 10.1084/jem.20170896 https://archive-ouverte.unige.ch/unige:109367

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Deposited on : 2018-10-18

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