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Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease
Graft‐versus‐host disease (GVHD) is a major life‐threatening complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Inflammatory signaling pathways promote T‐cell activation and are involved in the pathogenesis of GVHD. Suppressor of cytokine signaling 1 (SOCS1) is a critica...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313503/ https://www.ncbi.nlm.nih.gov/pubmed/35585676 http://dx.doi.org/10.1002/advs.202200978 |
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author | Guo, Huidong Li, Ruifeng Wang, Ming Hou, Yingping Liu, Shuoshuo Peng, Ting Zhao, Xiang‐Yu Lu, Liming Han, Yali Shao, Yiming Chang, Ying‐Jun Li, Cheng Huang, Xiao‐Jun |
author_facet | Guo, Huidong Li, Ruifeng Wang, Ming Hou, Yingping Liu, Shuoshuo Peng, Ting Zhao, Xiang‐Yu Lu, Liming Han, Yali Shao, Yiming Chang, Ying‐Jun Li, Cheng Huang, Xiao‐Jun |
author_sort | Guo, Huidong |
collection | PubMed |
description | Graft‐versus‐host disease (GVHD) is a major life‐threatening complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Inflammatory signaling pathways promote T‐cell activation and are involved in the pathogenesis of GVHD. Suppressor of cytokine signaling 1 (SOCS1) is a critical negative regulator for several inflammatory cytokines. However, its regulatory role in T‐cell activation and GVHD has not been elucidated. Multiomics analysis of the transcriptome and chromatin structure of granulocyte‐colony‐stimulating‐factor (G‐CSF)‐administered hyporesponsive T cells from healthy donors reveal that G‐CSF upregulates SOCS1 by reorganizing the chromatin structure around the SOCS1 locus. Parallel in vitro and in vivo analyses demonstrate that SOCS1 is critical for restraining T cell activation. Loss of Socs1 in T cells exacerbates GVHD pathogenesis and diminishes the protective role of G‐CSF in GVHD mouse models. Further analysis shows that SOCS1 inhibits T cell activation not only by inhibiting the colony‐stimulating‐factor 3 receptor (CSF3R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, but also by restraining activation of the inflammasome signaling pathway. Moreover, high expression of SOCS1 in T cells from patients correlates with low acute GVHD occurrence after HSCT. Overall, these findings identify that SOCS1 is critical for inhibiting T cell activation and represents a potential target for the attenuation of GVHD. |
format | Online Article Text |
id | pubmed-9313503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93135032022-07-27 Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease Guo, Huidong Li, Ruifeng Wang, Ming Hou, Yingping Liu, Shuoshuo Peng, Ting Zhao, Xiang‐Yu Lu, Liming Han, Yali Shao, Yiming Chang, Ying‐Jun Li, Cheng Huang, Xiao‐Jun Adv Sci (Weinh) Research Articles Graft‐versus‐host disease (GVHD) is a major life‐threatening complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Inflammatory signaling pathways promote T‐cell activation and are involved in the pathogenesis of GVHD. Suppressor of cytokine signaling 1 (SOCS1) is a critical negative regulator for several inflammatory cytokines. However, its regulatory role in T‐cell activation and GVHD has not been elucidated. Multiomics analysis of the transcriptome and chromatin structure of granulocyte‐colony‐stimulating‐factor (G‐CSF)‐administered hyporesponsive T cells from healthy donors reveal that G‐CSF upregulates SOCS1 by reorganizing the chromatin structure around the SOCS1 locus. Parallel in vitro and in vivo analyses demonstrate that SOCS1 is critical for restraining T cell activation. Loss of Socs1 in T cells exacerbates GVHD pathogenesis and diminishes the protective role of G‐CSF in GVHD mouse models. Further analysis shows that SOCS1 inhibits T cell activation not only by inhibiting the colony‐stimulating‐factor 3 receptor (CSF3R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, but also by restraining activation of the inflammasome signaling pathway. Moreover, high expression of SOCS1 in T cells from patients correlates with low acute GVHD occurrence after HSCT. Overall, these findings identify that SOCS1 is critical for inhibiting T cell activation and represents a potential target for the attenuation of GVHD. John Wiley and Sons Inc. 2022-05-18 /pmc/articles/PMC9313503/ /pubmed/35585676 http://dx.doi.org/10.1002/advs.202200978 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Guo, Huidong Li, Ruifeng Wang, Ming Hou, Yingping Liu, Shuoshuo Peng, Ting Zhao, Xiang‐Yu Lu, Liming Han, Yali Shao, Yiming Chang, Ying‐Jun Li, Cheng Huang, Xiao‐Jun Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease |
title | Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease |
title_full | Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease |
title_fullStr | Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease |
title_full_unstemmed | Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease |
title_short | Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease |
title_sort | multiomics analysis identifies socs1 as restraining t cell activation and preventing graft‐versus‐host disease |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313503/ https://www.ncbi.nlm.nih.gov/pubmed/35585676 http://dx.doi.org/10.1002/advs.202200978 |
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