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- W4313374427 abstract "Abstract Influenza (flu) infections cause 250,000 deaths and 3–5 million cases of severe illness during the average flu season. Severe influenza infections are associated with a combination of strong pro-inflammatory and weak anti-inflammatory immune responses. Production of the anti-inflammatory cytokine IL-10 by T cells restricts immunopathology during flu infections, however our knowledge of the signaling pathways regulating IL-10 induction is limited. Using IL-10GFP reporter mouse models, we found that Interleukin-2 inducible T cell kinase (ITK), a critical component in T cell receptor (TCR) signaling, regulates the development of IL-10-producing CD8+ T cells during influenza A infection. Compared to wild type (WT) mice, Itk−/− mice displayed increased morbidity and mortality after influenza infection, accompanied by a significant reduction of IL-10 producing CD8+ T cells in the airways. Using the model antigen ovalbumin (OVA) and transgenic TCR specific for OVA in CD8+ T cells (OTI), along with an allele sensitive mutation in the ITK kinase domain, we determine that ITK regulates IL-10 production in antigen-specific CD8+ T cells in a kinase dependent manner. RNA sequencing and multiparametric flow cytometric analyses revealed that ITK differentially regulates the expression of cell surface markers and transcription factors that are involved in regulating T cell differentiation, effector and memory phenotypes. Together, our data suggests that ITK is a critical regulator of IL-10 production by CD8+ T cells and regulate immunopathology during influenza infection. Modulating ITK signaling may be a strategy for regulating immunopathology due to viral infections." @default.
- W4313374427 created "2023-01-06" @default.
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- W4313374427 date "2020-05-01" @default.
- W4313374427 modified "2023-09-27" @default.
- W4313374427 title "ITK regulates IL-10 production by CD8+ T cells and lung immunopathology during influenza infection" @default.
- W4313374427 doi "https://doi.org/10.4049/jimmunol.204.supp.77.12" @default.
- W4313374427 hasPublicationYear "2020" @default.
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