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, Vol. 37, No. 15, 01.08.2018, p. e98615.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -