First Author | Moalli F | Year | 2018 |
Journal | J Exp Med | Volume | 215 |
Issue | 7 | Pages | 1869-1890 |
PubMed ID | 29875261 | Mgi Jnum | J:264049 |
Mgi Id | MGI:6192819 | Doi | 10.1084/jem.20170896 |
Citation | Moalli F, et al. (2018) The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8(+) T cells. J Exp Med 215(7):1869-1890 |
abstractText | 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. |