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Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb

Standard

Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb. / Xu, Yan; Pektor, Stefanie; Balkow, Sandra; Hemkemeyer, Sandra A; Liu, Zhijun; Grobe, Kay; Hanley, Peter J; Shen, Limei; Bros, Matthias; Schmidt, Talkea; Bähler, Martin; Grabbe, Stephan.

in: J IMMUNOL, Jahrgang 192, Nr. 8, 15.04.2014, S. 3559-68.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Xu, Y, Pektor, S, Balkow, S, Hemkemeyer, SA, Liu, Z, Grobe, K, Hanley, PJ, Shen, L, Bros, M, Schmidt, T, Bähler, M & Grabbe, S 2014, 'Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb', J IMMUNOL, Jg. 192, Nr. 8, S. 3559-68. https://doi.org/10.4049/jimmunol.1300695

APA

Xu, Y., Pektor, S., Balkow, S., Hemkemeyer, S. A., Liu, Z., Grobe, K., Hanley, P. J., Shen, L., Bros, M., Schmidt, T., Bähler, M., & Grabbe, S. (2014). Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb. J IMMUNOL, 192(8), 3559-68. https://doi.org/10.4049/jimmunol.1300695

Vancouver

Xu Y, Pektor S, Balkow S, Hemkemeyer SA, Liu Z, Grobe K et al. Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb. J IMMUNOL. 2014 Apr 15;192(8):3559-68. https://doi.org/10.4049/jimmunol.1300695

Bibtex

@article{e57b3bf76f5e4e1dae324c7d65419e73,
title = "Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb",
abstract = "Directed migration of stimulated dendritic cells (DCs) to secondary lymphoid organs and their interaction with Ag-specific T cells is a prerequisite for the induction of primary immune responses. In this article, we show that murine DCs that lack myosin IXB (Myo9b), a motorized negative regulator of RhoA signaling, exhibit increased Rho signaling activity and downstream acto-myosin contractility, and inactivation of the Rho target protein cofilin, an actin-depolymerizing factor. On a functional level, Myo9b(-/-) DCs showed impaired directed migratory activity both in vitro and in vivo. Moreover, despite unaltered Ag presentation and costimulatory capabilities, Myo9b(-/-) DCs were poor T cell stimulators in vitro in a three-dimensional collagen matrix and in vivo, associated with altered DC-T cell contact dynamics and T cell polarization. Accordingly, Myo9b(-/-) mice showed an attenuated ear-swelling response in a model of contact hypersensitivity. The impaired migratory and T cell stimulatory capacity of Myo9b(-/-) DCs was restored in large part by pharmacological activation of cofilin. Taken together, these results identify Myo9b as a negative key regulator of the Rho/RhoA effector Rho-kinase [Rho-associated coiled-coil-forming kinase (ROCK)]/LIM domain kinase signaling pathway in DCs, which controls cofilin inactivation and myosin II activation and, therefore may control, in part, the induction of adaptive immune responses. ",
keywords = "Actin Depolymerizing Factors/metabolism, Animals, Bone Marrow Cells/immunology, Cell Communication/immunology, Cell Differentiation, Cell Movement/immunology, Dendritic Cells/cytology, Dermatitis, Contact/genetics, GTPase-Activating Proteins/metabolism, Lymphocyte Activation/immunology, Mice, Mice, Knockout, Myosins/genetics, Signal Transduction, T-Lymphocyte Subsets/immunology, rho-Associated Kinases/metabolism",
author = "Yan Xu and Stefanie Pektor and Sandra Balkow and Hemkemeyer, {Sandra A} and Zhijun Liu and Kay Grobe and Hanley, {Peter J} and Limei Shen and Matthias Bros and Talkea Schmidt and Martin B{\"a}hler and Stephan Grabbe",
year = "2014",
month = apr,
day = "15",
doi = "10.4049/jimmunol.1300695",
language = "English",
volume = "192",
pages = "3559--68",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

RIS

TY - JOUR

T1 - Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the Rho-GTPase activating protein myosin IXb

AU - Xu, Yan

AU - Pektor, Stefanie

AU - Balkow, Sandra

AU - Hemkemeyer, Sandra A

AU - Liu, Zhijun

AU - Grobe, Kay

AU - Hanley, Peter J

AU - Shen, Limei

AU - Bros, Matthias

AU - Schmidt, Talkea

AU - Bähler, Martin

AU - Grabbe, Stephan

PY - 2014/4/15

Y1 - 2014/4/15

N2 - Directed migration of stimulated dendritic cells (DCs) to secondary lymphoid organs and their interaction with Ag-specific T cells is a prerequisite for the induction of primary immune responses. In this article, we show that murine DCs that lack myosin IXB (Myo9b), a motorized negative regulator of RhoA signaling, exhibit increased Rho signaling activity and downstream acto-myosin contractility, and inactivation of the Rho target protein cofilin, an actin-depolymerizing factor. On a functional level, Myo9b(-/-) DCs showed impaired directed migratory activity both in vitro and in vivo. Moreover, despite unaltered Ag presentation and costimulatory capabilities, Myo9b(-/-) DCs were poor T cell stimulators in vitro in a three-dimensional collagen matrix and in vivo, associated with altered DC-T cell contact dynamics and T cell polarization. Accordingly, Myo9b(-/-) mice showed an attenuated ear-swelling response in a model of contact hypersensitivity. The impaired migratory and T cell stimulatory capacity of Myo9b(-/-) DCs was restored in large part by pharmacological activation of cofilin. Taken together, these results identify Myo9b as a negative key regulator of the Rho/RhoA effector Rho-kinase [Rho-associated coiled-coil-forming kinase (ROCK)]/LIM domain kinase signaling pathway in DCs, which controls cofilin inactivation and myosin II activation and, therefore may control, in part, the induction of adaptive immune responses.

AB - Directed migration of stimulated dendritic cells (DCs) to secondary lymphoid organs and their interaction with Ag-specific T cells is a prerequisite for the induction of primary immune responses. In this article, we show that murine DCs that lack myosin IXB (Myo9b), a motorized negative regulator of RhoA signaling, exhibit increased Rho signaling activity and downstream acto-myosin contractility, and inactivation of the Rho target protein cofilin, an actin-depolymerizing factor. On a functional level, Myo9b(-/-) DCs showed impaired directed migratory activity both in vitro and in vivo. Moreover, despite unaltered Ag presentation and costimulatory capabilities, Myo9b(-/-) DCs were poor T cell stimulators in vitro in a three-dimensional collagen matrix and in vivo, associated with altered DC-T cell contact dynamics and T cell polarization. Accordingly, Myo9b(-/-) mice showed an attenuated ear-swelling response in a model of contact hypersensitivity. The impaired migratory and T cell stimulatory capacity of Myo9b(-/-) DCs was restored in large part by pharmacological activation of cofilin. Taken together, these results identify Myo9b as a negative key regulator of the Rho/RhoA effector Rho-kinase [Rho-associated coiled-coil-forming kinase (ROCK)]/LIM domain kinase signaling pathway in DCs, which controls cofilin inactivation and myosin II activation and, therefore may control, in part, the induction of adaptive immune responses.

KW - Actin Depolymerizing Factors/metabolism

KW - Animals

KW - Bone Marrow Cells/immunology

KW - Cell Communication/immunology

KW - Cell Differentiation

KW - Cell Movement/immunology

KW - Dendritic Cells/cytology

KW - Dermatitis, Contact/genetics

KW - GTPase-Activating Proteins/metabolism

KW - Lymphocyte Activation/immunology

KW - Mice

KW - Mice, Knockout

KW - Myosins/genetics

KW - Signal Transduction

KW - T-Lymphocyte Subsets/immunology

KW - rho-Associated Kinases/metabolism

U2 - 10.4049/jimmunol.1300695

DO - 10.4049/jimmunol.1300695

M3 - SCORING: Journal article

C2 - 24646736

VL - 192

SP - 3559

EP - 3568

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 8

ER -