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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Bibliographic Details
Published in:Frontiers in immunology 2018-11, 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: Article
Language:English
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
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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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.02521