Socs1-knockout in skin-resident CD4+ T cells in a protracted contact-allergic reaction results in an autonomous skin inflammation with features of early-stage mycosis fungoides

Luo, Y.X.; Vermeer, M.H.; Haan, S. de; Kinderman, P.; Gruijl, F.R. de; Hall, T. van; Tensen, C.P. (2023)

Article / Letter to editor

Recent detailed genomic analysis of mycosis fungoides (MF) identified suppressor of cytokine signaling 1 (SOCS1), an inhibitor of JAK/STAT signaling, as one of the frequently deleted tumor suppressors in MF, and one-copy deletion of SOCS1 was confirmed in early-stage MF lesions. To better understand the functional role of SOCS1 in the genesis of MF, we used a genetically engineered mouse model emulating heterozygous SOCS1 loss in skin resident CD4⁺ T cells. In these mice an experimentally induced contact-allergic reaction was maintained for 20 weeks. Ten weeks after discontinuing contact-allergic challenges, only the skin with locally one-copy deletion of Socs1 in CD4⁺ T cells still showed high numbers of CD3⁺/CD4⁺ Socs1 k.o. cells in the dermis (p ＜ 0.0001) with prevalent Stat3 activation (p ＜0.001). And in one out of 9 mice, this had progressed to far more dramatic increases, including the thickened epidermis, and with an explosive growth of Socs1 k.o. T cells in circulation; indicative of cutaneous lymphoma. Hence, we show that Socs1 mono-allelic loss in CD4⁺ T cells locally in protractedly inflamed skin results in autonomous skin inflammation with features of early-stage MF.

• Mycosis fungoides
• CD4(+) T cells
• Inflammation
• Transgenic mouse
• Socs1

• All authors: Luo, Y.X.; Vermeer, M.H.; Haan, S. de; Kinderman, P.; Gruijl, F.R. de; Hall, T. van; Tensen, C.P.
• Date: 2023-08-22
• Journal: BIOCHEMISTRY AND BIOPHYSICS REPORTS
• Volume: 35
• DOI: doi:10.1016/j.bbrep.2023.101535
• Link: https://www.sciencedirect.com/science/article/pii/S2405580823001164?via%...