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TC-PTP regulates the IL-7 transcriptional response during murine early T cell development

AuthorsPike, K.A.; Hatzihristidis, T.; Bussiéres-Marmen, S; Robert, F.; Desai, N.; Miranda-Saavedra, Diego; Pelletier, J.; Tremblay, M.L.
Issue Date16-Oct-2017
PublisherNature Publishing Group
CitationScientific Reports 7 (2017)
AbstractCytokines play a critical role in directing the discrete and gradual transcriptional changes that define T cell development. The interleukin-7 receptor (IL-7R), via its activation of the JAK-STAT pathway, promotes gene programs that change dynamically as cells progress through T cell differentiation. The molecular mechanism(s) directing differential gene expression downstream of the IL-7R are not fully elucidated. Here, we have identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as a negative regulator of IL-7R-STAT signaling in T cell progenitors, contributing to both the quantitative and qualitative nature of STAT-gene targeting. Novel genetic strategies used to modulate TC-PTP expression demonstrate that depletion of TC-PTP expression heightens the phosphorylation of STAT family members, causing aberrant expression of an interferon-response gene profile. Such molecular re-programming results in deregulation of early development checkpoints culminating in inefficient differentiation of CD4CD8 double positive cells. TC-PTP is therefore shown to be required to safeguard the dynamic transcriptome necessary for efficient T cell differentiation.
Identifiersdoi: 10.1038/s41598-017-13673-w
issn: 2045-2322
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