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

被引：4

作者：

Luo, Yixin ^{[1
]}

Vermeer, Maarten H. ^{[1
]}

de Haan, Sanne ^{[1
]}

Kinderman, Priscilla ^{[3
]}

de Gruijl, Frank R. ^{[1
]}

Van Hall, Thorbald ^{[2
]}

Tensen, Cornelis P. ^{[1
]}

机构：

[1] Leiden Univ Med Ctr, Dept Dermatol, Leiden, Netherlands

[2] Leiden Univ Med Ctr, Oncode Inst, Dept Med Oncol, Leiden, Netherlands

[3] Leiden Univ Med Ctr, Dept Gastroenterol & Hepatol, Leiden, Netherlands

来源：

BIOCHEMISTRY AND BIOPHYSICS REPORTS | 2023年 / 35卷

关键词：

Mycosis fungoides; CD4(+) T cells; Inflammation; Transgenic mouse; Socs1; ENGINEERED MOUSE MODELS; LYMPHOMA; EXPRESSION; CANCER; PROTEINS; PROFILE; SOCS1;

D O I：

10.1016/j.bbrep.2023.101535

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：8