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Research Overview

In 2012 Louis joined the laboratory of Prof. Talal Chatila at the Boston Children’s Hospital and Harvard Medical School to focus on fundamental molecular and cellular mechanism operative in immunological tolerance and the consequence of their breakdown in fostering human disease. He became an Instructor at the Department of Pediatrics, Harvard Medical School in 2016, with a long-term career goal of establishing an independent research program in cellular and molecular immunology to elucidate mechanisms of human immune dysregulatory diseases and develop curative therapies. In the process, Louis have made several key contributions to the field of immune dysregulation, including the elucidation of fundamental immune regulatory pathways involving Notch receptor signaling in regulatory T (Treg) cells that can be exploited for therapeutic purposes. Other contributions he made include the identification of LRBA deficiency as a novel cause of Treg cell deficiency, and the development of disease monitoring tools for heritable disorders of immune dysregulation, including LRBA, CTLA4 and STAT1 gain of function mutations.

 

Research Background

Louis-Marie Charbonnier studied cellular biology and physiology at Lyon University in France (2001-2003) and graduated from Montpellier University in molecular and cellular endocrinology (2004). He completed a PhD in immunology under the direction of Prof. Christian Jorgensen, during which time he worked on the development of therapeutic strategies using tolerogenic dendritic cells and regulatory T cells in a murine model of arthritis. His professional interest in immune dysregulation was further developed during post-doctoral studies under Prof. Alain Le Moine at the Institute for Medical Immunology, Free University of Brussels, in Belgium. During this post-doctoral position, Louis was able to publish in the field of Th17 and regulatory T cells and obtained rewards and grants for my studies during international congress and from Belgian national institutions.

 

Publications

  1. The 'Treg paradox' in inflammatory arthritis. Nat Rev Rheumatol. 2025 Jan; 21(1):9-21. View Abstract
  2. Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency. J Allergy Clin Immunol Glob. 2024 Nov; 3(4):100311. View Abstract
  3. The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2-associated multisystem inflammatory syndrome in children. J Clin Invest. 2023 01 03; 133(1). View Abstract
  4. A Stk4-Foxp3-NF-?B p65 transcriptional complex promotes Treg cell activation and homeostasis. Sci Immunol. 2022 09 23; 7(75):eabl8357. View Abstract
  5. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells. Immunity. 2022 07 12; 55(7):1173-1184.e7. View Abstract
  6. Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children. Res Sq. 2022 Apr 11. View Abstract
  7. Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency. J Clin Immunol. 2022 04; 42(3):634-652. View Abstract
  8. Large scale regulatory T cells screening. Allergy. 2022 02; 77(2):705-707. View Abstract
  9. Evolution and long-term outcomes of combined immunodeficiency due to CARMIL2 deficiency. Allergy. 2022 03; 77(3):1004-1019. View Abstract
  10. Author Correction: A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma. Nat Immunol. 2021 Jun; 22(6):794-795. View Abstract
  11. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination. J Exp Med. 2021 08 02; 218(8). View Abstract
  12. Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections. Immunity. 2021 06 08; 54(6):1186-1199.e7. View Abstract
  13. Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4+ T cell perturbations. Nat Immunol. 2021 05; 22(5):607-619. View Abstract
  14. Prostaglandin I2 signaling licenses Treg suppressive function and prevents pathogenic reprogramming. J Clin Invest. 2021 04 01; 131(7). View Abstract
  15. Essential functions of regulatory T cell TGF-ß1 revealed by differential gene-targeting approaches. Immunity. 2021 03 09; 54(3):397-398. View Abstract
  16. Stepwise Reversal of Immune Dysregulation Due to STAT1 Gain-of-Function Mutation Following Ruxolitinib Bridge Therapy and Transplantation. J Clin Immunol. 2021 05; 41(4):769-779. View Abstract
  17. Author Correction: A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma. Nat Immunol. 2021 Jan; 22(1):100. View Abstract
  18. Regulatory T Cell-Derived TGF-ß1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity. Immunity. 2020 Dec 15; 53(6):1331-1332. View Abstract
  19. The Transcription Factor Foxp3 Shapes Regulatory T Cell Identity by Tuning the Activity of trans-Acting Intermediaries. Immunity. 2020 11 17; 53(5):971-984.e5. View Abstract
  20. Regulatory T Cell-Derived TGF-ß1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity. Immunity. 2020 12 15; 53(6):1202-1214.e6. View Abstract
  21. A Patient with Novel ICOS Mutation Presented with Progressive Loss of B Cells. J Clin Immunol. 2021 01; 41(1):251-255. View Abstract
  22. A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma. Nat Immunol. 2020 11; 21(11):1359-1370. View Abstract
  23. Correction: Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome. J Exp Med. 2020 06 01; 217(7). View Abstract
  24. Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome. J Exp Med. 2020 06 01; 217(6). View Abstract
  25. Th17 reprogramming of T cells in systemic juvenile idiopathic arthritis. JCI Insight. 2020 03 26; 5(6). View Abstract
  26. Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma. J Allergy Clin Immunol. 2020 03; 145(3):897-906. View Abstract
  27. Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1. J Allergy Clin Immunol. 2020 01; 145(1):391-401.e8. View Abstract
  28. Regulatory T Cells: the Many Faces of Foxp3. J Clin Immunol. 2019 10; 39(7):623-640. View Abstract
  29. Functional reprogramming of regulatory T cells in the absence of Foxp3. Nat Immunol. 2019 09; 20(9):1208-1219. View Abstract
  30. Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms. Circulation. 2019 09 09; 140(10):846-863. View Abstract
  31. Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency. J Allergy Clin Immunol Pract. 2019 Nov - Dec; 7(8):2790-2800.e15. View Abstract
  32. Treatment of severe persistent asthma with IL-6 receptor blockade. J Allergy Clin Immunol Pract. 2019 May - Jun; 7(5):1639-1642.e4. View Abstract
  33. Hematopoietic Stem Cell Transplantation in Patients with Heterozygous STAT1 Gain-of-Function Mutation. J Clin Immunol. 2019 01; 39(1):37-44. View Abstract
  34. EROS/CYBC1 mutations: Decreased NADPH oxidase function and chronic granulomatous disease. J Allergy Clin Immunol. 2019 02; 143(2):782-785.e1. View Abstract
  35. Oral immunotherapy with omalizumab reverses the Th2 cell-like programme of regulatory T cells and restores their function. Clin Exp Allergy. 2018 07; 48(7):825-836. View Abstract
  36. DOCK8 Deficiency Presenting as an IPEX-Like Disorder. J Clin Immunol. 2017 Nov; 37(8):811-819. View Abstract
  37. Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation. J Allergy Clin Immunol. 2018 03; 141(3):1050-1059.e10. View Abstract
  38. CTLA-4 haploinsufficiency in a patient with an autoimmune lymphoproliferative disorder. J Allergy Clin Immunol. 2017 09; 140(3):862-864.e4. View Abstract
  39. Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J Allergy Clin Immunol. 2017 May; 139(5):1629-1640.e2. View Abstract
  40. An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells. Nat Med. 2016 09; 22(9):1013-22. View Abstract
  41. Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1. J Clin Immunol. 2016 10; 36(7):641-8. View Abstract
  42. Dedicator of cytokinesis 8 regulates signal transducer and activator of transcription 3 activation and promotes TH17 cell differentiation. J Allergy Clin Immunol. 2016 11; 138(5):1384-1394.e2. View Abstract
  43. Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling. Nat Immunol. 2015 Nov; 16(11):1162-73. View Abstract
  44. MyD88 Adaptor-Dependent Microbial Sensing by Regulatory T Cells Promotes Mucosal Tolerance and Enforces Commensalism. Immunity. 2015 Aug 18; 43(2):289-303. View Abstract
  45. Renal involvement in the immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) disorder. Pediatr Nephrol. 2015 Jul; 30(7):1197-202. View Abstract
  46. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015 Mar 17; 42(3):512-23. View Abstract
  47. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol. 2015 Jan; 135(1):217-27. View Abstract
  48. The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity. PLoS One. 2013; 8(11):e79984. View Abstract
  49. IL-17A and IL-2-expanded regulatory T cells cooperate to inhibit Th1-mediated rejection of MHC II disparate skin grafts. PLoS One. 2013; 8(10):e76040. View Abstract
  50. Interferon regulatory factor 3 controls interleukin-17 expression in CD8 T lymphocytes. Proc Natl Acad Sci U S A. 2013 Aug 20; 110(34):E3189-97. View Abstract
  51. IL-17A mediates early post-transplant lesions after heterotopic trachea allotransplantation in Mice. PLoS One. 2013; 8(7):e70236. View Abstract
  52. Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease. Am J Transplant. 2013 Mar; 13(3):611-20. View Abstract
  53. IL-10 produced by induced regulatory T cells (iTregs) controls colitis and pathogenic ex-iTregs during immunotherapy. J Immunol. 2012 Dec 15; 189(12):5638-48. View Abstract
  54. Impact of interleukin-2-expanded regulatory T cells in various allogeneic combinations on mouse skin graft survival. Transplant Proc. 2012 Nov; 44(9):2840-4. View Abstract
  55. CTLA4-Ig restores rejection of MHC class-II mismatched allografts by disabling IL-2-expanded regulatory T cells. Am J Transplant. 2012 Sep; 12(9):2313-21. View Abstract
  56. Rapamycin as immunosuppressant in murine transplantation model. Methods Mol Biol. 2012; 821:435-45. View Abstract
  57. Critical role of regulatory T cells in Th17-mediated minor antigen-disparate rejection. J Immunol. 2010 Sep 15; 185(6):3417-25. View Abstract
  58. Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis. J Autoimmun. 2010 Jun; 34(4):390-9. View Abstract
  59. A brief focus on memory cells in transplantation. Transplant Proc. 2009 Oct; 41(8):3361-2. View Abstract
  60. Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1. Am J Transplant. 2009 Sep; 9(9):2034-47. View Abstract
  61. [Involvement of natural regulatory lymphocytes in allograft tolerance]. Bull Mem Acad R Med Belg. 2009; 164(5-6):230-9. View Abstract
  62. Interleukin 17-producing T helper cells in alloimmunity. Transplant Rev (Orlando). 2009 Jan; 23(1):11-8. View Abstract
  63. CD8+ T-Cell depletion and rapamycin synergize with combined coreceptor/stimulation blockade to induce robust limb allograft tolerance in mice. Am J Transplant. 2008 Dec; 8(12):2527-36. View Abstract
  64. Immunomodulatory dendritic cells inhibit Th1 responses and arthritis via different mechanisms. J Immunol. 2007 Aug 01; 179(3):1506-15. View Abstract
  65. Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells. 2007 Aug; 25(8):2025-32. View Abstract
  66. Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells. J Immunol. 2006 Sep 15; 177(6):3806-13. View Abstract
  67. Heterogeneity of avenin, the oat prolamin. Fractionation, molecular weight and amino acid composition. Biochim Biophys Acta. 1978 Nov 20; 537(1):22-30. View Abstract

Contact Louis-Marie Charbonnier

Phone: 617-919-8775
Fax: 617-730-0528