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Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney

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Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney. / Viau, Amandine; Bienaimé, Frank; Lukas, Kamile; Todkar, Abhijeet P; Knoll, Manuel; Yakulov, Toma A; Hofherr, Alexis; Kretz, Oliver; Helmstädter, Martin; Reichardt, Wilfried; Braeg, Simone; Aschman, Tom; Merkle, Annette; Pfeifer, Dietmar; Dumit, Verónica I; Gubler, Marie-Claire; Nitschke, Roland; Huber, Tobias B; Terzi, Fabiola; Dengjel, Jörn; Grahammer, Florian; Köttgen, Michael; Busch, Hauke; Boerries, Melanie; Walz, Gerd; Triantafyllopoulou, Antigoni; Kuehn, E Wolfgang.

in: EMBO J, Jahrgang 37, Nr. 15, 01.08.2018, S. e98615.

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

Harvard

Viau, A, Bienaimé, F, Lukas, K, Todkar, AP, Knoll, M, Yakulov, TA, Hofherr, A, Kretz, O, Helmstädter, M, Reichardt, W, Braeg, S, Aschman, T, Merkle, A, Pfeifer, D, Dumit, VI, Gubler, M-C, Nitschke, R, Huber, TB, Terzi, F, Dengjel, J, Grahammer, F, Köttgen, M, Busch, H, Boerries, M, Walz, G, Triantafyllopoulou, A & Kuehn, EW 2018, 'Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney', EMBO J, Jg. 37, Nr. 15, S. e98615. https://doi.org/10.15252/embj.201798615

APA

Viau, A., Bienaimé, F., Lukas, K., Todkar, A. P., Knoll, M., Yakulov, T. A., Hofherr, A., Kretz, O., Helmstädter, M., Reichardt, W., Braeg, S., Aschman, T., Merkle, A., Pfeifer, D., Dumit, V. I., Gubler, M-C., Nitschke, R., Huber, T. B., Terzi, F., ... Kuehn, E. W. (2018). Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney. EMBO J, 37(15), e98615. https://doi.org/10.15252/embj.201798615

Vancouver

Viau A, Bienaimé F, Lukas K, Todkar AP, Knoll M, Yakulov TA et al. Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney. EMBO J. 2018 Aug 1;37(15):e98615. https://doi.org/10.15252/embj.201798615

Bibtex

@article{cc113976e7a74491bf04adede8590acf,
title = "Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney",
abstract = "Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy-related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell-autonomous manner and results in peritubular accumulation of CCR2+ mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis.",
keywords = "Journal Article",
author = "Amandine Viau and Frank Bienaim{\'e} and Kamile Lukas and Todkar, {Abhijeet P} and Manuel Knoll and Yakulov, {Toma A} and Alexis Hofherr and Oliver Kretz and Martin Helmst{\"a}dter and Wilfried Reichardt and Simone Braeg and Tom Aschman and Annette Merkle and Dietmar Pfeifer and Dumit, {Ver{\'o}nica I} and Marie-Claire Gubler and Roland Nitschke and Huber, {Tobias B} and Fabiola Terzi and J{\"o}rn Dengjel and Florian Grahammer and Michael K{\"o}ttgen and Hauke Busch and Melanie Boerries and Gerd Walz and Antigoni Triantafyllopoulou and Kuehn, {E Wolfgang}",
note = "{\textcopyright} 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",
year = "2018",
month = aug,
day = "1",
doi = "10.15252/embj.201798615",
language = "English",
volume = "37",
pages = "e98615",
journal = "EMBO J",
issn = "0261-4189",
publisher = "NATURE PUBLISHING GROUP",
number = "15",

}

RIS

TY - JOUR

T1 - Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney

AU - Viau, Amandine

AU - Bienaimé, Frank

AU - Lukas, Kamile

AU - Todkar, Abhijeet P

AU - Knoll, Manuel

AU - Yakulov, Toma A

AU - Hofherr, Alexis

AU - Kretz, Oliver

AU - Helmstädter, Martin

AU - Reichardt, Wilfried

AU - Braeg, Simone

AU - Aschman, Tom

AU - Merkle, Annette

AU - Pfeifer, Dietmar

AU - Dumit, Verónica I

AU - Gubler, Marie-Claire

AU - Nitschke, Roland

AU - Huber, Tobias B

AU - Terzi, Fabiola

AU - Dengjel, Jörn

AU - Grahammer, Florian

AU - Köttgen, Michael

AU - Busch, Hauke

AU - Boerries, Melanie

AU - Walz, Gerd

AU - Triantafyllopoulou, Antigoni

AU - Kuehn, E Wolfgang

N1 - © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy-related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell-autonomous manner and results in peritubular accumulation of CCR2+ mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis.

AB - Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy-related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell-autonomous manner and results in peritubular accumulation of CCR2+ mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis.

KW - Journal Article

U2 - 10.15252/embj.201798615

DO - 10.15252/embj.201798615

M3 - SCORING: Journal article

C2 - 29925518

VL - 37

SP - e98615

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 15

ER -