A Critical Role for IL-17RB Signaling in HTLV-1 Tax-Induced NF-κB Activation and T-Cell Transformation


The retrovirus HTLV-1 is the causative agent of an aggressive lymphoproliferative disorder known as adult T-cell leukemia (ATL). The HTLV-1 Tax regulatory protein constitutively activates the host NF-κB transcription factor to promote T-cell proliferation, survival and cell transformation. However, it remains unknown precisely how Tax persistently activates NF-κB in T cells. In this study, we used next-generation sequencing to identify genes that were differentially expressed upon HTLV-1 infection and immortalization of primary T cells. We found that IL-17RB, the receptor for the IL-25 cytokine, was highly induced in HTLV-1 transformed T cells and was required for NF-κB activation, cell proliferation and survival. Tax induced the expression of IL-17RB and established a positive feedback loop together with IL-25 that triggered persistent NF-κB activation and the upregulation of IL-9 and other genes critical for T-cell proliferation and survival. IL-17RB was also overexpressed in a subset of acute ATL patient specimens and therefore may potentially be targeted by monoclonal antibodies as a novel ATL therapy.


Vyšlo v časopise: A Critical Role for IL-17RB Signaling in HTLV-1 Tax-Induced NF-κB Activation and T-Cell Transformation. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004418
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004418

Souhrn

The retrovirus HTLV-1 is the causative agent of an aggressive lymphoproliferative disorder known as adult T-cell leukemia (ATL). The HTLV-1 Tax regulatory protein constitutively activates the host NF-κB transcription factor to promote T-cell proliferation, survival and cell transformation. However, it remains unknown precisely how Tax persistently activates NF-κB in T cells. In this study, we used next-generation sequencing to identify genes that were differentially expressed upon HTLV-1 infection and immortalization of primary T cells. We found that IL-17RB, the receptor for the IL-25 cytokine, was highly induced in HTLV-1 transformed T cells and was required for NF-κB activation, cell proliferation and survival. Tax induced the expression of IL-17RB and established a positive feedback loop together with IL-25 that triggered persistent NF-κB activation and the upregulation of IL-9 and other genes critical for T-cell proliferation and survival. IL-17RB was also overexpressed in a subset of acute ATL patient specimens and therefore may potentially be targeted by monoclonal antibodies as a novel ATL therapy.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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