Human inherited CCR2 deficiency underlies progressive polycystic lung disease

• DOI: 10.1016/j.cell.2023.11.036
• Publication Date: 2023-12-28T15:28:07Z
• Authors: Anna-Lena Neehus; Brenna Carey; Marija Landekic; Patricia Panikulam; Gail Deutsch; Masato Ogishi; Carlos A. Arango-...; Quentin Philippot; Mohammadreza Moda...; Iraj Mohammadzadeh; Melissa Corcini B...; Darawan Rinchai; Tom Le Voyer; Jérémie Rosain; Mana Momenilandi; Marta Martin-Fern...; Taushif Khan; Jonathan Bohlen; Ji Eun Han; Alexandre Deslys; Mathilde Bernard; Tania Gajardo-Car...; Camille Soudée; Corentin Le Floc’h; Mélanie Migaud; Yoann Seeleuthner; Mi-Sun Jang; Eirini Nikolouli; Simin Seyedpour; Hugues Begueret; Jean-François Emile; Pierre Le Guen; Guido Tavazzi; Costanza Natalia ...; Federico Capra Ma...; Micol Angelini; Francesca Trespidi; Stefano Ghirardello; Nasrin Alipour; Anne Molitor; Raphael Carapito; Mohsen Mazloomrezaei; Hassan Rokni-Zadeh; Majid Changi-Asht...; Chantal Brouzes; Pablo Vargas; Alessandro Borghesi; Nico Lachmann; Seiamak Bahram; Bruno Crestani; Michael Fayon; François Galode; Susanta Pahari; Larry S. Schlesinger; Nico Marr; Dusan Bogunovic; Stéphanie Boisson...; Vivien Béziat; Laurent Abel; Raphael Borie; Lisa R. Young; Robin Deterding; Mohammad Shahrooei; Nima Rezaei; Nima Parvaneh; Daniel Craven; Philippe Gros; Danielle Malo; Fernando E. Sepul...; Lawrence M. Nogee; Nathalie Aladjidi; Bruce C. Trapnell; Jean-Laurent Casa...; Jacinta Bustamante
• Keywords: Pulmonary and Respiratory Medicine; Receptors, CCR2; Chemokine receptor; Human Inborn Errors; Immunology; 610; Trained Immunity in Health and Disease; macrophage; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; Pulmonary Alveolar Proteinosis; Alveolar; Monocyte; Article; 618; cystic lung disease; Receptors; Sciences du Vivant [q-bio]/Biologie cellulaire; Macrophages, Alveolar; Health Sciences; Humans; chemotaxis; Child; Neonatal Lung Development and Respiratory Morbidity; Biology; Lung; Internal medicine; Immunology and Microbiology; JGM; Macrophages; Genetic Basis of Primary Immunodeficiency Disorders; FOS: Clinical medicine; Life Sciences; PAP; Immune system; Chemokine; Reinfection; monocyte; Medicine; CCR2; recurrent infection; Pulmonary alveolar proteinosis

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients compound heterozygous three, all loss-of-expression loss-of-function. They abolish CCR2-agonist ligand (CCL-2)-stimulated Ca2+ signaling migration monocytic cells. All high blood CCL-2 levels, providing diagnostic test for screening with unexplained or mycobacterial Blood myeloid lymphoid subsets interferon (IFN)-γ- granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity unaffected. CCR2-deficient monocytes macrophage-like cells normal gene expression profiles functions. By contrast, macrophage counts about half. Human is genetic etiology PAP, infections impaired CCL2-dependent to lungs infected tissues.