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
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580823001164 |
| _version_ | 1797660329430220800 |
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| author | Yixin Luo Maarten H. Vermeer Sanne de Haan Priscilla Kinderman Frank R. de Gruijl Thorbald van Hall Cornelis P. Tensen |
| author_facet | Yixin Luo Maarten H. Vermeer Sanne de Haan Priscilla Kinderman Frank R. de Gruijl Thorbald van Hall Cornelis P. Tensen |
| author_sort | Yixin Luo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:28:15Z |
| format | Article |
| id | doaj.art-b9355e1eca9f464bb2d0eb5d5e974c60 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-03-11T18:28:15Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-b9355e1eca9f464bb2d0eb5d5e974c602023-10-13T13:55:01ZengElsevierBiochemistry and Biophysics Reports2405-58082023-09-0135101535Socs1-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 fungoidesYixin Luo0Maarten H. Vermeer1Sanne de Haan2Priscilla Kinderman3Frank R. de Gruijl4Thorbald van Hall5Cornelis P. Tensen6Department of Dermatology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Dermatology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Dermatology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Dermatology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Dermatology, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405580823001164Mycosis fungoidesCD4+ T cellsInflammationTransgenic mouseSocs1 |
| spellingShingle | Yixin Luo Maarten H. Vermeer Sanne de Haan Priscilla Kinderman Frank R. de Gruijl Thorbald van Hall Cornelis P. Tensen 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 Biochemistry and Biophysics Reports Mycosis fungoides CD4+ T cells Inflammation Transgenic mouse Socs1 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Mycosis fungoides CD4+ T cells Inflammation Transgenic mouse Socs1 |
| url | http://www.sciencedirect.com/science/article/pii/S2405580823001164 |
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