Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell-mediated graft-versus-host disease

Détails

ID Serval
serval:BIB_00458044C63F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell-mediated graft-versus-host disease
Périodique
Am J Respir Crit Care Med
Auteur(s)
Mauermann N., Burian J., von Garnier C., Dirnhofer S., Germano D., Schuett C., Tamm M., Bingisser R., Eriksson U., Hunziker L.
ISSN
1535-4970 (Electronic)
ISSN-L
1073-449X
Statut éditorial
Publié
Date de publication
2008
Volume
178
Numéro
4
Pages
379-88
Langue
anglais
Notes
Mauermann, Nora
Burian, Julia
von Garnier, Christophe
Dirnhofer, Stefan
Germano, Davide
Schuett, Christine
Tamm, Michael
Bingisser, Roland
Eriksson, Urs
Hunziker, Lukas
eng
Research Support, Non-U.S. Gov't
Am J Respir Crit Care Med. 2008 Aug 15;178(4):379-88. doi: 10.1164/rccm.200711-1648OC. Epub 2008 May 29.
Résumé
RATIONALE: Pulmonary complications of hematopoietic stem cell transplantation include infections and graft-versus-host diseases, such as idiopathic pneumonia syndrome (IPS). Conflicting data exist regarding the role of the interferon (IFN)-gamma-producing Th1 CD4(+) T-cell subset and IL-17A in IPS. OBJECTIVES: To determine the role of IFN-gamma and IL-17A in the establishment of pulmonary graft-versus-host disease. METHODS: A semiallogeneic murine model based on C57BL/6 x BALB/c as recipients with transplantation of BALB/c RAG2(-/-) bone marrow and transfer of different genetic knockout T cells (T-bet(-/-), IFN-gamma(-/-), IFN-gammaR(-/-)) on a BALB/c background. Lung tissue was examined for parenchymal changes and infiltrating cells by histology and fluorescence-activated cell sorter analysis. MEASUREMENTS AND MAIN RESULTS: After transfer of semiallogeneic bone marrow together with donor CD4(+) T cells lacking IFN-gamma or T-bet-a T-box transcription factor controlling Th1 commitment-we found severe inflammation in the lungs, but no enhancement in other organs. In contrast, wild-type donor CD4(+) T cells mediated minimal inflammation only, and donor CD8(+) T cells were not required for IPS development. Mechanistically, the absence of IFN-gamma or IFN-gamma signaling in pulmonary parenchymal cells promoted expansion of IL-17A-producing CD4(+) T cells and local IL-17A release. In vivo depletion of IL-17A reduced disease severity. CONCLUSIONS: One mechanism of IFN-gamma protection against IPS is negative regulation of the expansion of pathogenic IL-17A-producing CD4(+) T cells through interaction with the IFN-gamma receptor on the pulmonary parenchymal cell population.
Mots-clé
Animals, Bone Marrow Transplantation/*immunology/pathology, CD4-Positive T-Lymphocytes/*immunology, *Disease Models, Animal, Graft vs Host Disease/*immunology/pathology, Interferon-gamma/*physiology, Interleukin-17/*blood, Lung/immunology/pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Pneumonia/*immunology/pathology, Receptors, Interferon/physiology, Syndrome, T-Box Domain Proteins/physiology, Th1 Cells/*immunology
Pubmed
Création de la notice
15/04/2021 9:58
Dernière modification de la notice
01/05/2021 5:33
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