1. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8 T cells
- Author
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Mykhailo Vladymyrov, Ruth Lyck, Michael Sixt, Xenia Ficht, Alba Diz-Muñoz, Jasmin Balmer, Martin Bähler, Ingrid de Vries, Bettina Stolp, Matteo Iannacone, Jens V. Stein, Federica Moalli, Amleto Fiocchi, Doron Merkler, Michael Hubert Stoffel, Mario Kreutzfeldt, Akitaka Ariga, James Sharpe, Philipp Germann, 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, M. H., Sharpe, J., Bahler, M., Sixt, M., Diz-Munoz, A., and Stein, J. V.
- Subjects
0301 basic medicine ,rho GTP-Binding Proteins ,Lymphoid Tissue ,530 Physics ,T cell ,Immunology ,Receptors, Lymphocyte Homing ,chemical and pharmacologic phenomena ,610 Medicine & health ,ddc:616.07 ,CD8-Positive T-Lymphocytes ,Myosins ,Lymphocyte Activation ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Movement ,Cell polarity ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Cytoskeleton ,Cells, Cultured ,Research Articles ,Cell Proliferation ,Epidermis (botany) ,Chemistry ,Cell growth ,Immunity ,Cell Polarity ,Cell biology ,Extracellular Matrix ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,570 Life sciences ,biology ,Epidermis ,CD8 ,030215 immunology - Abstract
Moalli et al. combine in vitro CD8+ T cell motility analysis with intravital imaging of mouse tissues to identify the actomyosin regulator Myo9b as a central player for nonlymphoid tissue infiltration during adaptive immune responses by facilitating crossing of tissue barriers., 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.
- Published
- 2018