95 : Type I interferon regulates acute IL-5 and IL-13 expression in human memory CD4+ T cells

• Published in: Cytokine (Philadelphia, Pa.) Vol. 63; no. 3; p. 265
• Main Authors: Gonzales-van Horn, Sarah R., Huber, Jonathan P., David Farrar, J.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.09.2013
• Subjects: asthma; CD4-positive T-lymphocytes; gene expression; hepatitis C; human development; humans; interferons; interleukin-13; interleukin-4; interleukin-5; sclerosis; translation (genetics)
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2013.06.098

Type I Interferon (IFN-α/β) is a critical anti-viral cytokine and is currently being used to treat Hepatitis C viral infections and multiple sclerosis, among other diseases. Although the positive regulatory effects of this cytokine have been studied, less is known about its role as a negative regulator of gene expression. Previously, we demonstrated that IFN-α/β suppresses Th2 development in human naïve CD4+ T cells by negatively regulating GATA3 expression, leading to the suppression of IL-4, IL-5 and IL-13. Based on this data, we were interested in how IFN-α/β might affect other T cell types. In the current study, we interrogated the effects of IFN-α/β on human memory CD4+ T cells. We hypothesized that IFN-α/β has similar negative regulatory effects on memory CD4+ T cells, leading to decreased Th2 cytokine expression. Human memory CD4+ T cells were acutely stimulated in the presence of IFN-α. Interestingly, IL-5 and IL-13 gene expression was suppressed, however, IL-4 expression was unaffected. Further, IFN-α/β signaling, but not IFN-γ or IFN-λ, suppressed IL-5 and IL-13 expression. Nuclear run-on studies demonstrated that IFN-α/β signaling suppressed de novo transcription of IL-5 and IL-13, and this suppression did not require the translation of interferon-sensitive genes. Our data indicate that this negative regulatory pathway acted upstream of gene expression, and suggested that IFN-α/β was able to acutely suppress specific gene expression. Currently, we are assessing direct STAT2 binding by ChIP-Seq, which will identify potential cis-regulatory regions necessary for IL-5 and L-13 gene modulation. Together, these results suggest that IFN-α/β could have many benefits in suppressing multiple aspects of Th2 development and effector function in atopic asthma.