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Comment
. 2020 Mar;140(3):713-716.
doi: 10.1016/j.jid.2019.07.714. Epub 2019 Aug 26.

Low SATB1 Expression Promotes IL-5 and IL-9 Expression in Sézary Syndrome

Alberto Herrera  1 , Simon Fredholm  2 , Anthony Cheng  3 , Eleni P Mimitou  4 , Angelina Seffens  5 , Michal Bar-Natan  6 , Amy Sun  1 , Jo-Ann Latkowski  7 , Andreas Willerslew-Olsen  2 , Terkild B Buus  2 , Maria Gluud  2 , Thorbjørn Krejsgaard  2 , Sara Torres-Rusillo  2 , Charlotte Menné Bonefeld  2 , Anders Woetmann  2 , Carsten Geisler  2 , Larisa J Geskin  8 , Zhengqing Ouyang  3 , Peter Smibert  4 , Niels Ødum  9 , Sergei B Koralov  10
Affiliations
Comment

Low SATB1 Expression Promotes IL-5 and IL-9 Expression in Sézary Syndrome

Alberto Herrera et al. J Invest Dermatol. 2020 Mar.
No abstract available

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Conflict of interest statement

CONFLICT OF INTEREST

Peter Smibert is an author on a patent disclosing the Cellular Indexing of Transcriptomes and Epitopes by sequencing methods used in the study. The rest of the authors state no conflict of interest.

Figures

Figure 1.
Figure 1.. Malignant T cells display low SATB1 expression.
(a, b) Bar graphs: Normalized counts from bulk RNA sequencing analysis comparing sorted (a) naive Th versus malignant SS cells and (b) memory T-helper versus malignant SS cells. T-helper naive cells (n = 3) and memory T cells (n = 4) were sorted from healthy individuals, and malignant cells (n = 7) were sorted based on expression of CD3 and CD4 and lack of or low expression of CD7 and CD26 in malignant T cells as described in Fanok et al., 2018. (c) Bar graphs showing relative expression from bulk sorted and sequenced CD4+ Th cells and SS cells from Wang et al., 2015.(d) Representative t-SNE plot showing transcriptome-based clustering and levels of SATB1 expression (blue) in PBMCs from a patient with SS. Clonal malignant CD4+ T cells (1352) expressing TRAV 35: CAGQLRNAGGTSYGKLTF and TRBV 20–1: CSARFLRGGYNEQFF are encased in pink, whereas polyclonal non-malignant CD4+ T cells (1025) are encased in green. (e) Scatter plot showing frequency of clonal malignant (black) and polyclonal non-malignant (grey) CD4+ T cells from 2 patients with SS and CD4+ T cells (white) from 2 healthy individuals with normalized SATB1 expression > 1.0. A total of 29 of 1352 and 18 of 1730 total malignant cells had SATB1 expression > 1.0, whereas 337 of 1025 and 357 of 1288 non-malignant cells and 308 of 1089 and 387 of 1331 total CD4+ T cells from 2 healthy individuals were above that threshold. CTRL, control; PBMC, peripheral blood mononuclear cells; SATB1, special AT-rich sequence-binding protein-1; SS, Sézary syndrome; Th, T helper; t-SNE, t-distributed stochastic neighbor embedding.
Figure 2.
Figure 2.. Inhibition of SATB1 promotes expression of IL-5 and IL-9.
The malignant SS cell line SeAx was treated with (a) siRNA against SATB1 or non-target control or (b) antagomir-155 or antagomir control. RNA was purified 48 hours after treatment, and gene expression was analyzed by qPCR with GAPDH as control. Results are shown as relative values to expression in non-target controls arbitrarily defined as 1. GAPDH, glyceraldehyde-3-phosphate dehydrogenase; qPCR, quantitative reverse transcriptase in real time; SATB1, special AT-rich sequence-binding protein-1; SS, Sézary syndrome; siRNA, small interfering RNA.
See this image and copyright information in PMC

Comment on

References

    1. Buus TB, Willerslev-Olsen A, Fredholm S, Blümel E, Nastasi C, Gluud M, et al. Single-cell heterogeneity in Sezary syndrome. Blood Adv 2018;2:2115–26. - PMC - PubMed
    1. Fanok MH, Sun A, Fogli LK, Narendran V, Eckstein M, Kannan K, et al. Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of cutaneous T-cell lymphoma. J Invest Dermatol 2018;138:1116–25. - PMC - PubMed
    1. Fredholm S, Willerslev-Olsen A, Met Ö, Kubat L, Gluud M, Mathiasen SL, et al. SATB1 in malignant T cells. J Invest Dermatol 2018;138:1805–15. - PubMed
    1. Gagat M, Grzanka D, Krajewski A. Ambiguous role of SATB1 expression in malignant tumors. J Invest Dermatol 2019;139:1608–10. - PubMed
    1. Gao Y, Sun J, Yi S, Tu P, Wang Y. Response to the commentary “Ambiguous role of SATB1 expression in malignant tumors”. J Invest Dermatol 2019;139:1611–2.

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