Journal
EMBO JOURNAL
Volume 37, Issue 15, Pages -Publisher
WILEY
DOI: 10.15252/embj.201798615
Keywords
cilia; macrophages; nephronophthisis; polycystic kidney disease
Categories
Funding
- ARC Foundation
- ERA-EDTA [ALTF 84-2011]
- FRM [ARF20150934110]
- EMBO [ALTF 927-2013]
- Else Kroner-Fresenius-Stiftung [2011_A87]
- Deutsche Forschungsgemeinschaft [KFO 201, KU 1504/5-1, 1504/7-1, SFB1140, SFB1160, CRC1140, CRC 992, HU 1016/8-1, EXC306/2]
- Heisenberg program, BMBF [01GM1518C]
- European Research Council (ERC) [616891]
- H2020-IMI2 consortium BEAt-DKD
- German Federal Ministry of Education and Research (BMBF) [FKZ 01ZX1409B]
- [SFB 1140]
- [SFB 152]
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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.
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