Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1869-1890 |
| Number of pages | 22 |
| Journal | Journal of Experimental Medicine |
| Volume | 215 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2018 |
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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 journal › Article
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TY - JOUR
T1 - The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells
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
Y1 - 2018
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.
U2 - 10.1084/jem.20170896
DO - 10.1084/jem.20170896
M3 - Article
VL - 215
SP - 1869
EP - 1890
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 7
ER -