Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft-Versus-Host Disease

Adv Sci (Weinh). 2022 Jul;9(21):e2200978. doi: 10.1002/advs.202200978. Epub 2022 May 18.


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.

Keywords: SOCS1; T cell tolerance; graft-versus-host disease (GVHD); hematopoietic stem cell transplantation (HSCT); multiomics.

MeSH terms

  • Animals
  • Chromatin
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / genetics
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Mice
  • Suppressor of Cytokine Signaling 1 Protein* / genetics
  • Systems Biology / methods
  • T-Lymphocytes* / metabolism
  • Transplantation, Homologous / adverse effects


  • Chromatin
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Granulocyte Colony-Stimulating Factor