Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA

Shuai Li; Bastian Dislich; Cord H Brakebusch; Stefan F Lichtenthaler; Thomas Brocker

doi:10.4049/jimmunol.1500676

Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA

Shuai Li, Bastian Dislich, Cord H Brakebusch, Stefan F Lichtenthaler, Thomas Brocker

1 Citationer (Scopus)

Abstract

Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation.

Originalsprog	Engelsk
Tidsskrift	Journal of immunology (Baltimore, Md. : 1950)
Vol/bind	195
Udgave nummer	9
Sider (fra-til)	4244-56
Antal sider	13
ISSN	0022-1767
DOI	https://doi.org/10.4049/jimmunol.1500676
Status	Udgivet - 1 nov. 2015

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10.4049/jimmunol.1500676

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title = "Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA",

abstract = "Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation.",

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author = "Shuai Li and Bastian Dislich and Brakebusch, {Cord H} and Lichtenthaler, {Stefan F} and Thomas Brocker",

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AU - Li, Shuai

AU - Dislich, Bastian

AU - Brakebusch, Cord H

AU - Lichtenthaler, Stefan F

AU - Brocker, Thomas

PY - 2015/11/1

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N2 - Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation.

AB - Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation.

KW - Animals

KW - Antigens, CD11c

KW - Apoptosis

KW - Blotting, Western

KW - Bone Marrow Cells

KW - Cell Proliferation

KW - Cell Survival

KW - Cells, Cultured

KW - Cytokinesis

KW - Dendritic Cells

KW - Flow Cytometry

KW - Homeostasis

KW - Membrane Proteins

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Phosphatidylinositol 3-Kinases

KW - Proto-Oncogene Proteins c-akt

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Spleen

KW - bcl-Associated Death Protein

KW - rhoA GTP-Binding Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.4049/jimmunol.1500676

M3 - Journal article

C2 - 26408665

SN - 0022-1767

VL - 195

SP - 4244

EP - 4256

JO - Journal of Immunology

JF - Journal of Immunology

IS - 9

ER -

Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA

Abstract

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