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Flt3l Governs the Development of Partially Overlapping Hematopoietic Lineages in Humans and Mice Publisher Pubmed



Momenilandi M1, 2 ; Levy R1, 2, 3 ; Sobrino S4, 5 ; Li J6, 7 ; Lagreslepeyrou C2, 8 ; Esmaeilzadeh H9, 10 ; Fayand A1, 2, 11 ; Le Floch C1, 2 ; Guerin A12, 13 ; Mina ED12, 13 ; Shearer D6, 7 ; Delmonte OM14 ; Yatim A15 ; Mulder K16, 17 Show All Authors
Authors
  1. Momenilandi M1, 2
  2. Levy R1, 2, 3
  3. Sobrino S4, 5
  4. Li J6, 7
  5. Lagreslepeyrou C2, 8
  6. Esmaeilzadeh H9, 10
  7. Fayand A1, 2, 11
  8. Le Floch C1, 2
  9. Guerin A12, 13
  10. Mina ED12, 13
  11. Shearer D6, 7
  12. Delmonte OM14
  13. Yatim A15
  14. Mulder K16, 17
  15. Mancini M18, 19
  16. Rinchai D15
  17. Denis A5
  18. Neehus AL1, 2
  19. Balogh K6, 7
  20. Brendle S6, 7, 20
  21. Roknizadeh H21
  22. Changiashtiani M22
  23. Seeleuthner Y1, 2
  24. Deswarte C1, 2
  25. Bessot B2, 8
  26. Cremades C1
  27. Materna M1, 2
  28. Cederholm A23
  29. Ogishi M15
  30. Philippot Q1, 2
  31. Beganovic O24
  32. Ackermann M25, 26, 27
  33. Wuyts M28
  34. Khan T29
  35. Fouere S30
  36. Herms F31
  37. Chanal J32
  38. Palterer B14
  39. Bruneau J33
  40. Molina TJ33
  41. Leclercmercier S33
  42. Pretet JL34
  43. Youssefian L35
  44. Vahidnezhad H36, 37, 38
  45. Parvaneh N39
  46. Claeys KG40, 41
  47. Schrijvers R42
  48. Luka M43
  49. Perot P44
  50. Fourgeaud J45, 46
  51. Nourrisson C47, 48
  52. Poirier P47, 48
  53. Jouanguy E1, 2, 15
  54. Boissondupuis S1, 2, 15
  55. Bustamante J1, 2, 15, 49
  56. Notarangelo LD14
  57. Christensen N6, 7
  58. Landegren N23, 50
  59. Abel L1, 2, 15
  60. Marr N29, 51
  61. Six E8
  62. Langlais D18, 19, 52
  63. Waterboer T53
  64. Ginhoux F16, 17
  65. Ma CS12, 13
  66. Tangye SG12, 13
  67. Meyts I54, 55
  68. Lachmann N25, 26, 27
  69. Hu J6, 7
  70. Shahrooei M28, 56
  71. Bossuyt X28, 57
  72. Casanova JL1, 2, 3, 15, 58
  73. Beziat V1, 2, 15
Show Affiliations
Authors Affiliations
  1. 1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France
  2. 2. Paris Cite University, Imagine Institute, Paris, France
  3. 3. Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France
  4. 4. Laboratory of Chromatin and Gene Regulation During Development, Paris Cite University, UMR1163 INSERM, Imagine Institute, Paris, France
  5. 5. Laboratory of Human Lymphohematopoiesis, INSERM, Imagine Institute, Paris, France
  6. 6. Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, PA, United States
  7. 7. Department of Pathology and Laboratory Medicine, Pennsylvania State University College of Medicine, Hershey, PA, United States
  8. 8. Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France
  9. 9. Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  10. 10. Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
  11. 11. Sorbonne University, AP-HP, Tenon Hospital, Department of Internal Medicine, Paris, France
  12. 12. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  13. 13. St. Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW, Australia
  14. 14. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
  15. 15. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, United States
  16. 16. Gustave Roussy Cancer Campus, Villejuif, France
  17. 17. Paris-Saclay University, Ile-de-France, France
  18. 18. Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, QC, Canada
  19. 19. Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
  20. 20. Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, United States
  21. 21. Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran
  22. 22. School of Mathematics, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
  23. 23. Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
  24. 24. Laboratoire d'Onco-hematologie, Necker Hospital for Sick Children, AP-HP, Paris, France
  25. 25. Hannover Medical School, Department of Pediatric Pulmonology, Allergology and Neonatology, Hannover, Germany
  26. 26. Hannover Medical School, Cluster of Excellence RESIST (EXC 2155), Hannover, Germany
  27. 27. Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany
  28. 28. Department of Microbiology and Immunology, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium
  29. 29. Research Branch, Sidra Medicine, Doha, Qatar
  30. 30. Groupe Hospitalier Saint-Louis, Lariboisiere, Fernand-Widal, CeGIDD, AP-HP, Paris, France
  31. 31. Dermatology Department, Paris-Cite University, INSERM 976, Saint Louis Hospital, Paris, France
  32. 32. Dermatology Department, Cochin Hospital, INSERM U1016, AP-HP, Paris, France
  33. 33. Department of Pathology, Necker Hospital for Sick Children, AP-HP, Paris-Cite University, Paris, France
  34. 34. Papillomavirus National Reference Center, Besancon Hospital, Besancon, France
  35. 35. Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
  36. 36. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
  37. 37. Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
  38. 38. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
  39. 39. Department of Pediatrics, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  40. 40. Department of Neurology, University Hospitals Leuven, Leuven, Belgium
  41. 41. Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Leuven, Belgium
  42. 42. Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium
  43. 43. Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, Paris, 75015, France
  44. 44. Pathogen Discovery Laboratory, Institut Pasteur, Paris Cite University, Paris, France
  45. 45. Paris Cite University, URP 7328 FETUS, Paris, France
  46. 46. Microbiology Department, AP-HP, Necker Hospital for Sick Children, Paris, France
  47. 47. Clermont Auvergne University, INSERM U1071, M2iSH, USC INRAE 1382, CHU Clermont-Ferrand, 3IHP, Department of Parasitology-Mycology, Clermont-Ferrand, France
  48. 48. National Reference Center for Cryptosporidiosis, Microsporidia and Other Digestive Protozoa, Clermont-Ferrand, France
  49. 49. Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France
  50. 50. Centre for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  51. 51. College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
  52. 52. Department of Human Genetics, McGill University, Montreal, QC, Canada
  53. 53. Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
  54. 54. Laboratory of Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
  55. 55. Department of Pediatrics, Leuven University Hospitals, Leuven, Belgium
  56. 56. Specialized Immunology Laboratory of Dr. Shahrooei, Tehran, Iran
  57. 57. Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
  58. 58. Howard Hughes Medical Institute, New York, NY, United States

Source: Cell Published:2024


Abstract

FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients’ bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients’ blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells. © 2024 The Authors
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