Constitutive expression of IRF-5 in HTLV-1-infected T cells

Abstract

Abstract. Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive and fatal leukemia of T cells. Interferon regulatory factor (IRF)-5 plays a critical role in the induction of interferon genes in viral infected cells. We examined the specific mechanisms underlying the expression and regulation of IRF-5 in HTLV-1-infected T cells. IRF-5 was constitutively transcribed into three distinct alternatively spliced isoforms (V1, V3 and V4) in HTLV-1-infected T-cell lines but not in uninfected T-cell lines. IRF-5 was also upregulated in HTLV-1-infected T-cell lines at protein level. Nuclear IRF-5 expression was noted in ATL cells present in lymph nodes and skin lesions. IRF-5 mRNA expression was induced following infection of T cells with HTLV-1, and specifically by viral oncoprotein Tax. Tax also activated V3 promoter. Microarray analysis of IRF-5-expressing uninfected T cells demonstrated that IRF-5 induced the expression of tumor necrosis factor family cytokines. The results suggest that IRF-5 is a Tax-regulated gene, and its expression may be associated with the pathogenesis of ATL.

T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation

“…These T cell outcomes have been thought to be indirect and attributed to the altered responses in IRF5 À/À myeloid cells that serve as antigen-presenting cells (Alzaid et al, 2016;Byrne et al, 2017;Krausgruber et al, 2011;Oriss et al, 2017;Xu et al, 2017). This interpretation was supported by the initial failure to detect IRF5 expression in T cells (Mancl et al, 2005), although subsequent studies identified IRF5 expression in activated T cells (Griesbeck et al, 2015;Ishikawa et al, 2015). A recent study found that during chronic Leishmania donovani infection, IRF5 expression was upregulated in T cells in a Toll-like receptor 7 (TLR7)-dependent manner and that T cell-intrinsic IRF5 contributed to T cell death after long-term infection (Fabié et al, 2018).…”

Specific detection of interferon regulatory factor 5 (IRF5): A case of antibody inequality

“…Surprisingly, we have found that some companies used Jurkat T cells as a positive control for IRF5 protein detection; to our knowledge, there have been no publications showing IRF5 expression in Jurkat cells. To the contrary, two recent publications have shown that Jurkat T cells lack IRF5 expression 36 37 . Furthermore, analysis of Jurkat RNAseq reads from ENCODE using the UCSC Genome Browser indicate that Jurkat cells either express too low IRF5 that reads are not detected across exons or expression is absent 38 39 .…”

An overview of the human immune system and the role of interferon regulatory factors (IRFs)

“…Perhaps because early studies reported that expression of IRF5 is barely detected in T cell [46] . Nonetheless, recent studies have detected elevated IRF5 expression in parasitic and viral infected T cells [47,48] and have highlighted its direct role in a T cell subset during chronic parasitic infection [49] . Fabié et al (2018) [49] demonstrated that TLR-7 mediated activation of IRF5 promoted IFNγ + CD4 T cell death because of its ability to enhance death receptor 5 (DR5)-induction cell apoptosis in CD4 T, thus promoting persistent L. donovani infection.…”