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

F Moalli, X Ficht, P Germann, M Vladymyrov, B Stolp, I De Vries, R Lyck, J Balmer, A Fiocchi, M Kreutzfeldt, D Merkler, M Iannacone, A Ariga, MH Stoffel, J Sharpe, M Bähler, M Sixt, A Diz‑Muñoz, JV Stein

Research output: Contribution to journalArticle

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. © 2018 Moalli et al.
Original languageEnglish
Pages (from-to)1869-1890
Number of pages22
JournalJournal of Experimental Medicine
Volume215
Issue number7
DOIs
Publication statusPublished - 2018

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Myosins
T-Lymphocytes
Tissue Expansion
Actomyosin
Monomeric GTP-Binding Proteins
Lymphoid Tissue
Dermis
Infection Control
Guanosine Triphosphate
Cytoskeleton
Basement Membrane
Epidermis
Lymphocytes
Skin

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Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., De Vries, I., ... Stein, JV. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. Journal of Experimental Medicine, 215(7), 1869-1890. https://doi.org/10.1084/jem.20170896

The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. / 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, MH; Sharpe, J; Bähler, M; Sixt, M; Diz‑Muñoz, A; Stein, JV.

In: Journal of Experimental Medicine, Vol. 215, No. 7, 2018, p. 1869-1890.

Research output: Contribution to journalArticle

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, MH, Sharpe, J, Bähler, M, Sixt, M, Diz‑Muñoz, A & Stein, JV 2018, 'The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells', Journal of Experimental Medicine, vol. 215, no. 7, pp. 1869-1890. https://doi.org/10.1084/jem.20170896
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, MH ; Sharpe, J ; Bähler, M ; Sixt, M ; Diz‑Muñoz, A ; Stein, JV. / The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 7. pp. 1869-1890.
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AU - Moalli, F

AU - Ficht, X

AU - Germann, P

AU - Vladymyrov, M

AU - Stolp, B

AU - De Vries, I

AU - Lyck, R

AU - Balmer, J

AU - Fiocchi, A

AU - Kreutzfeldt, M

AU - Merkler, D

AU - Iannacone, M

AU - Ariga, A

AU - Stoffel, MH

AU - Sharpe, J

AU - Bähler, M

AU - Sixt, M

AU - Diz‑Muñoz, A

AU - Stein, JV

PY - 2018

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N2 - 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. © 2018 Moalli et al.

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. © 2018 Moalli et al.

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