The many roles of TOX in the immune system

Aliahmad, Parinaz; Seksenyan, Akop; Kaye, Jonathan

doi:10.1016/j.coi.2011.12.001

Cited by 94 publications

(70 citation statements)

References 37 publications

(66 reference statements)

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“…Id2 has already been discovered as one central hub for ILC fate and NFIL3 and TOX may be other candidates. The DNA binding factor TOX is an interesting candidate because Tox −/− mice lack NK cell and ILC3 development (Aliahmad et al, 2012; Geiger et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Development, Differentiation, and Diversity of Innate Lymphoid Cells

Diefenbach¹,

2014

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Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILC). ILC are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILC has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILC can be grouped into two separate lineages, cytotoxic ILC represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILC (i.e., ILC1, ILC2, ILC3). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and T cell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces.

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Section: Discussionmentioning

confidence: 99%

Development, Differentiation, and Diversity of Innate Lymphoid Cells

Diefenbach¹,

2014

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“…[13][14][15]30,31 The roles of TOX in immune system development are relatively wellcharacterized since its discovery 13 ; however, its role in human cancer has not been reported. On the basis of our findings, TOX has emerged as a key player, when expressed ectopically, in driving malignant cell transformation in CTCL.…”

Section: Discussionmentioning

confidence: 99%

“…Mice deficient in TOX failed to develop CD4 1 T-cell lineage; however, on the newly formed CD4 1 T cells exiting the thymus, TOX is tightly downregulated and remains suppressed in the mature CD4 1 T cells in the skin and blood. [13][14][15] Therefore, the observation of TOX expression in MF skin biopsy specimens is highly unusual. Whether TOX contributes to CTCL pathogenesis has not been investigated.…”

Section: Cd45romentioning

confidence: 99%

Evidence of an oncogenic role of aberrant TOX activation in cutaneous T-cell lymphoma

Huang

Jiang

et al. 2015

Blood

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“…Malignant CTCL cells were identified both by CD4 positivity and TOX expression. [49][50][51] Indeed, TOX is only expressed by ;60% of CD4 1 T cells in skin biopsies from patients with confirmed CTCL diagnosis, and it is not expressed by NS or skin from AD ( Figure 1B-C), a benign inflammatory skin condition that presents some clinical and histologic features common to CTCL 50,52 and harbors a large number of infiltrating CD4…”

Section: Il-13 In the Pathogenesis Of Ctcl 2799mentioning

confidence: 99%

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation

Geskin¹,

Viragova²,

Stolz

et al. 2015

Blood

132

113

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Key Points• IL-13 is an autocrine factor for CTCL.• IL-13 and its receptors represent novel markers of CTCL malignancy and potential therapeutic targets for intervention.Cutaneous T-cell lymphomas (CTCLs) primarily affect skin and are characterized by proliferation of mature CD4 1 T-helper cells. The pattern of cytokine production in the skin and blood is considered to be of major importance for the pathogenesis of CTCLs. Abnormal cytokine expression in CTCLs may be responsible for enhanced proliferation of the malignant cells and/or depression of the antitumor immune response. Here we show that interleukin-13 (IL-13) and its receptors IL-13Ra1 and IL-13Ra2 are highly expressed in the clinically involved skin of CTCL patients. We also show that malignant lymphoma cells, identified by the coexpression of CD4 and TOX (thymus high-mobility group box), in the skin and blood of CTCL patients produce IL-13 and express both receptors. IL-13 induces CTCL cell growth in vitro and signaling through the IL-13Ra1. Furthermore, antibody-mediated neutralization of IL-13 or soluble IL-13Ra2 molecules can lead to inhibition of tumor-cell proliferation, implicating IL-13 as an autocrine factor in CTCL. Importantly, we established that IL-13 synergizes with IL-4 in inhibiting CTCL cell growth and that blocking the IL-4/IL-13 signaling pathway completely reverses tumor-cell proliferation. We conclude that IL-13 and its signaling mediators are novel markers of CTCL malignancy and potential therapeutic targets for intervention. (Blood. 2015;125(18):2798-2805

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The many roles of TOX in the immune system

Cited by 94 publications

References 37 publications

Development, Differentiation, and Diversity of Innate Lymphoid Cells

Development, Differentiation, and Diversity of Innate Lymphoid Cells

Evidence of an oncogenic role of aberrant TOX activation in cutaneous T-cell lymphoma

Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation

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