Non-apoptotic Fas (CD95) Signaling on T Cells Regulates the Resolution of Th2-Mediated Inflammation

Fas (CD95/APO-1) and its ligand (FasL/CD95L) promote the resolution of type 2 lung inflammation and eosinophilia. We previously found that Fas-deficiency on T cells, but not eosinophils, delayed resolution of inflammation. However, Fas can signal both cell death and have a positive signaling functio...

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Published inFrontiers in immunology Vol. 9; p. 2521
Main Authors Williams, Jesse W., Ferreira, Caroline M., Blaine, Kelly M., Rayon, Crystal, Velázquez, Francisco, Tong, Jiankun, Peter, Marcus E., Sperling, Anne I.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 01.11.2018
Subjects
allergy
Animals
Apoptosis
Apoptosis - immunology
Asthma
Eosinophilia
fas Receptor - immunology
Fas-FasL
Immunology
Inflammation Mediators - immunology
Mice
Mice, Inbred C57BL
Pneumonia - immunology
Signal Transduction - immunology
T-Lymphocytes - immunology
Th2 cells
Th2 Cells - immunology
allergy
Th2 cells
Eosinophilia
Fas-FasL
Apoptosis
Asthma
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Summary:Fas (CD95/APO-1) and its ligand (FasL/CD95L) promote the resolution of type 2 lung inflammation and eosinophilia. We previously found that Fas-deficiency on T cells, but not eosinophils, delayed resolution of inflammation. However, Fas can signal both cell death and have a positive signaling function that can actually activate cells. In this study, we investigated whether Fas-induced death or Fas-activated signaling pathways promote resolution of allergic lung inflammation. By increasing T cell survival through two Fas-independent pathways, using Bim-deficient T cells or Bcl-x overexpressing T cells, no differences in resolution of Th2-mediated inflammation was observed. Furthermore, Th2 cells were inherently resistant to Fas-mediated apoptosis and preferentially signaled through non-apoptotic pathways following FasL treatment. Utilizing Fas-mutant mice deficient in apoptotic but sufficient for non-apoptotic Fas signaling pathways, we demonstrate that non-apoptotic Fas signaling in T cells drives resolution of Th2-mediated airway inflammation. Our findings reveal a previously unknown role for non-apoptotic Fas signaling on Th2 cells in the induction of resolution of type 2 inflammation.
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This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
These authors have contributed equally to this work
Reviewed by: David Chaplin, University of Alabama at Birmingham, United States; Joan Clària, Hospital Clínic de Barcelona, Spain
Caroline M. Ferreira, Institute of Environmental, Chemistry and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, Brazil
Francisco Velázquez, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
Edited by: Praveen Akuthota, University of California, San Diego, United States
Present Address: Jesse W. Williams, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.02521