Abstract |
Innate lymphoid cells (ILCs) are critical mediators of mucosal immunity, and group 1 ILCs (ILC1 cells) and group 3 ILCs (ILC3 cells) have been shown to be functionally plastic. Here we found that group 2 ILCs (ILC2 cells) also exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ (IFN-γ). Interleukin 12 (IL-12) and IL-18 regulated this conversion, and during viral infection, ILC2 cells clustered within inflamed areas and acquired an ILC1-like phenotype. Mechanistically, these ILC1 cells augmented virus-induced inflammation in a manner dependent on the transcription factor T-bet. Notably, IL-12 converted human ILC2 cells into ILC1 cells, and the frequency of ILC1 cells in patients with chronic obstructive pulmonary disease ( COPD) correlated with disease severity and susceptibility to exacerbations. Thus, functional plasticity of ILC2 cells exacerbates anti-viral immunity, which may have adverse consequences in respiratory diseases such as COPD.
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Authors | Jonathan S Silver, Jennifer Kearley, Alan M Copenhaver, Caroline Sanden, Michiko Mori, Li Yu, Gretchen Harms Pritchard, Aaron A Berlin, Christopher A Hunter, Russell Bowler, Jonas S Erjefalt, Roland Kolbeck, Alison A Humbles |
Journal | Nature immunology
(Nat Immunol)
Vol. 17
Issue 6
Pg. 626-35
(06 2016)
ISSN: 1529-2916 [Electronic] United States |
PMID | 27111143
(Publication Type: Journal Article)
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Chemical References |
- Cytokines
- GATA3 Transcription Factor
- Gata3 protein, mouse
- Inflammation Mediators
- T-Box Domain Proteins
- T-box transcription factor TBX21
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Topics |
- Aged
- Animals
- Cell Differentiation
- Cell Plasticity
(immunology)
- Cells, Cultured
- Cytokines
(metabolism)
- Female
- GATA3 Transcription Factor
(genetics, metabolism)
- Gene Expression Regulation
- Haemophilus Infections
(immunology)
- Haemophilus influenzae
(immunology)
- Humans
- Immunity, Innate
- Inflammation Mediators
(metabolism)
- Influenza A virus
(immunology)
- Lung
(immunology)
- Lymphocytes
(immunology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Middle Aged
- Orthomyxoviridae Infections
(immunology)
- Phenotype
- Pulmonary Disease, Chronic Obstructive
(immunology)
- Smoking
(adverse effects)
- Staphylococcal Infections
(immunology)
- Staphylococcus aureus
(immunology)
- T-Box Domain Proteins
(genetics, metabolism)
- Th1 Cells
(immunology)
- Th2 Cells
(immunology)
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