Document Type
Article
Publication Date
1-18-2024
Original Citation
Neehus A,
Carey B,
Landekic M,
Panikulam P,
Deutsch G,
Ogishi M,
Arango-Franco C,
Philippot Q,
Modaresi M,
Mohammadzadeh I,
Corcini Berndt M,
Rinchai D,
Le Voyer T,
Rosain J,
Momenilandi M,
Martin-Fernandez M,
Khan T,
Bohlen J,
Han J,
Deslys A,
Bernard M,
Gajardo-Carrasco T,
Soudée C,
Le Floc'h C,
Migaud M,
Seeleuthner Y,
Jang M,
Nikolouli E,
Seyedpour S,
Begueret H,
Emile J,
Le Guen P,
Tavazzi G,
Colombo C,
Marzani F,
Angelini M,
Trespidi F,
Ghirardello S,
Alipour N,
Molitor A,
Carapito R,
Mazloomrezaei M,
Rokni-Zadeh H,
Changi-Ashtiani M,
Brouzes C,
Vargas P,
Borghesi A,
Lachmann N,
Bahram S,
Crestani B,
Pahari S,
Schlesinger L,
Marr N,
Bugonovic D,
Boisson-Dupuis S,
Béziat V,
Abel L,
Borie R,
Young L,
Deterding R,
Shahrooei M,
Rezaei N,
Parvaneh N,
Craven D,
Gros P,
Malo D,
Sepulveda F,
Nogee L,
Aladjidi N,
Trapnell B,
Casanova J,
Bustamante J.
Human inherited CCR2 deficiency underlies progressive polycystic lung disease. Cell. 2024;187(2):390-408 e23.
Keywords
JGM, Child, Humans, Lung, Macrophages, Alveolar, Pulmonary Alveolar Proteinosis, Receptors, CCR2, Reinfection
JAX Source
Cell. 2024;187(2):390-408 e23.
ISSN
1097-4172
PMID
38157855
DOI
https://doi.org/10.1016/j.cell.2023.11.036
Abstract
We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Gue ́ rin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2- agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-g- and granulocyte- macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient mono- cytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.
Comments
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).