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Human Inherited Ccr2 Deficiency Underlies Progressive Polycystic Lung Disease Publisher Pubmed



Neehus AL1, 2 ; Carey B3, 63 ; Landekic M4 ; Panikulam P5 ; Deutsch G6 ; Ogishi M7 ; Arangofranco CA1, 2, 8 ; Philippot Q1, 2 ; Modaresi M9, 61 ; Mohammadzadeh I10, 60 ; Corcini Berndt M1, 2 ; Rinchai D7 ; Le Voyer T1, 2 ; Rosain J1, 2, 11 Show All Authors
Authors
  1. Neehus AL1, 2
  2. Carey B3, 63
  3. Landekic M4
  4. Panikulam P5
  5. Deutsch G6
  6. Ogishi M7
  7. Arangofranco CA1, 2, 8
  8. Philippot Q1, 2
  9. Modaresi M9, 61
  10. Mohammadzadeh I10, 60
  11. Corcini Berndt M1, 2
  12. Rinchai D7
  13. Le Voyer T1, 2
  14. Rosain J1, 2, 11
  15. Momenilandi M1, 2
  16. Martinfernandez M12, 13, 14, 15, 16
  17. Khan T62
  18. Bohlen J1, 2
  19. Han JE7
  20. Deslys A18
  21. Bernard M18, 19, 20
  22. Gajardocarrasco T5
  23. Soudee C1, 2
  24. Le Floch C1, 2
  25. Migaud M1, 2
  26. Seeleuthner Y1, 2
  27. Jang MS21
  28. Nikolouli E21
  29. Seyedpour S22, 23
  30. Begueret H24
  31. Emile JF25
  32. Le Guen P26
  33. Tavazzi G27, 28
  34. Colombo CNJ28, 29
  35. Marzani FC28
  36. Angelini M30
  37. Trespidi F30
  38. Ghirardello S30
  39. Alipour N31, 32
  40. Molitor A31, 32
  41. Carapito R31, 32, 33
  42. Mazloomrezaei M34
  43. Roknizadeh H35
  44. Changiashtiani M36
  45. Brouzes C37
  46. Vargas P18, 19, 20
  47. Borghesi A30, 38
  48. Lachmann N21, 39, 40, 41
  49. Bahram S31, 32, 33
  50. Crestani B26
  51. Pahari S42
  52. Schlesinger LS42
  53. Marr N17, 43, 44
  54. Bugonovic D12, 13, 14, 15, 16
  55. Boissondupuis S1, 2, 7
  56. Beziat V1, 2, 7
  57. Abel L1, 2, 7
  58. Borie R26
  59. Young LR45
  60. Deterding R46
  61. Shahrooei M34, 47
  62. Rezaei N22, 48, 49
  63. Parvaneh N50
  64. Craven D51
  65. Gros P52, 53
  66. Malo D4, 54
  67. Sepulveda FE5
  68. Nogee LM55
  69. Aladjidi N56
  70. Trapnell BC3, 57
  71. Casanova JL1, 2, 7, 58, 59
  72. Bustamante J1, 2, 7, 11
Show Affiliations
Authors Affiliations
  1. 1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, 75015, France
  2. 2. Paris Cite University, Imagine Institute, Paris, 75015, France
  3. 3. Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, 45229, OH, United States
  4. 4. Department of Medicine, McGill University, Montreal, H3G 0B1, QC, Canada
  5. 5. Molecular Basis of Altered Immune Homeostasis, INSERM U1163, Paris Cite University, Imagine Institute, Paris, 75015, France
  6. 6. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, 98195, WA, United States
  7. 7. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, 10065, NY, United States
  8. 8. Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia, Medellin, Colombia
  9. 9. Pediatric Pulmonary and Sleep Medicine Department, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Non-communicable Pediatric Diseases Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  11. 11. Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, 75015, France
  12. 12. Center for Inborn Errors of Immunity, Icahn School, New York, 10029, NY, United States
  13. 13. Precision Immunology Institute, Icahn School, New York, 10029, NY, United States
  14. 14. Mindich Child Health and Development Institute, Icahn School, New York, 10029, NY, United States
  15. 15. Department of Pediatrics, Icahn School, New York, 10029, NY, United States
  16. 16. Department of Microbiology, Icahn School, New York, 10029, NY, United States
  17. 17. Department of Human Immunology, Sidra Medicine, Doha, Qatar
  18. 18. Leukomotion Laboratory, Paris Cite University, INSERM UMR-S1151, CNRS UMR-S8253, Necker Hospital for Sick Children, Paris, 75015, France
  19. 19. Curie Institute, PSL Research University, CNRS, UMR144, Paris, 75248, France
  20. 20. Pierre-Gilles de Gennes Institute, PSL Research University, Paris, 75005, France
  21. 21. Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, 30625, Germany
  22. 22. Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran
  23. 23. Nanomedicine Research Association (NRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  24. 24. Department of Pathology, Haut-Leveque Hospital, CHU Bordeaux, Pessac, 33604, France
  25. 25. Pathology Department, Ambroise-Pare Hospital, AP-HP, Boulogne, 92100, France
  26. 26. Pulmonology Service, Bichat Hospital, AP-HP and Paris Cite University, INSERM U1152, PHERE, Paris, 75018, France
  27. 27. Department of Surgical, Pediatric, and Diagnostic Sciences, University of Pavia, Pavia, 27100, Italy
  28. 28. Anesthesia and Intensive Care, San Matteo Research Hospital, Pavia, 27100, Italy
  29. 29. Experimental Medicine, University of Pavia, Pavia, 27100, Italy
  30. 30. Neonatal Intensive Care Unit, San Matteo Research Hospital, Pavia, 27100, Italy
  31. 31. Molecular Immuno-Rheumatology Laboratory, INSERM UMR_S1109, GENOMAX Platform, Faculty of Medicine, OMICARE University Hospital Federation, Immunology and Hematology Research Center, Research Center in Biomedicine of Strasbourg (CRBS), Federation of Translational Medicine of Strasbourg (FMTS), University of Strasbourg, Strasbourg, 67081, France
  32. 32. Interdisciplinary Thematic Institute (ITI) of Precision Medicine of Strasbourg, University of Strasbourg, Strasbourg, 67081, France
  33. 33. Immunology Laboratory, Biology Technical Platform, Biology Pole, New Civil Hospital, Strasbourg, 67091, France
  34. 34. Dr. Shahrooei Laboratory, 22 Bahman St., Ashrafi Esfahani Blvd, Tehran, Iran
  35. 35. Department of Medical Biotechnology, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran
  36. 36. School of Mathematics, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
  37. 37. Laboratory of Onco-Hematology, Necker Hospital for Sick Children, Paris, 75015, France
  38. 38. School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, 1015, Switzerland
  39. 39. REBIRTH - Research Center for Translational Regenerative Medicine, Hannover, 30625, Germany
  40. 40. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, 30625, Germany
  41. 41. Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, 30625, Germany
  42. 42. Host-Pathogen Interactions and Population Health programs, Texas Biomedical Research Institute, San Antonio, 78227, TX, United States
  43. 43. College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
  44. 44. Institute of Translational Immunology, Brandenburg Medical School, Brandenburg, 14770, Germany
  45. 45. Division of Pulmonary and Sleep Medicine, Children's Hospital of Philadelphia, Philadelphia, 19104, PA, United States
  46. 46. Pediatric Pulmonary Medicine, Children's Hospital Colorado, Aurora, 80045, CO, United States
  47. 47. Clinical and Diagnostic Immunology, KU Leuven, Leuven, 3000, Belgium
  48. 48. Network of Immunity to Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  49. 49. Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran
  50. 50. Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
  51. 51. Division of Pediatric Pulmonology, Rainbow Babies and Children's Hospital, Cleveland, 44106, OH, United States
  52. 52. Department of Microbiology and Immunology, McGill University, Montreal, H3A 2B4, QC, Canada
  53. 53. Department of Biochemistry, McGill University, Montreal, H3A 2B4, QC, Canada
  54. 54. Department of Human Genetics, McGill University, Montreal, H3G 0B1, QC, Canada
  55. 55. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, 21205, MD, United States
  56. 56. Pediatric Oncology Hematology Unit, Clinical Investigation Center (CIC), Multi-theme-CIC (CICP), University Hospital Bordeaux, Bordeaux, 33000, France
  57. 57. Departments of Medicine and Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, 45267, OH, United States
  58. 58. Howard Hughes Medical Institute, New York, 10065, NY, United States
  59. 59. Department of Pediatrics, Necker Hospital for Sick Children, Paris, 75015, France
  60. 60. USERN Office, Babol University of Medical Sciences, Babol, Iran
  61. 61. Pediatric Pulmonary Disease and Sleep Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Science, Tehran, Iran
  62. 62. The Jackson Laboratory, Farmington, 06032, CT, United States
  63. 63. Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, 45267, OH, United States

Source: Cell Published:2024


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 Guerin (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)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes 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. © 2023 The Author(s)
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