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

Yixin Luo; Maarten H Vermeer; Sanne de Haan; Priscilla Kinderman; Frank R de Gruijl; Thorbald van Hall; Cornelis P Tensen

doi:10.1016/j.bbrep.2023.101535

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

Biochem Biophys Rep. 2023 Aug 22:35:101535. doi: 10.1016/j.bbrep.2023.101535. eCollection 2023 Sep.

Authors

Yixin Luo¹, Maarten H Vermeer¹, Sanne de Haan¹, Priscilla Kinderman², Frank R de Gruijl¹, Thorbald van Hall³, Cornelis P Tensen¹

Affiliations

¹ Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
² Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
³ Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands.

Abstract

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.

Keywords: CD4+ T cells; Inflammation; Mycosis fungoides; Socs1; Transgenic mouse.