SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development

Yu Gao, Ruining Liu, Chenfei He, Juan Basile, Mattias Vesterlund, Marie Wahren-Herlenius, Alexander Espinoza, Cassandra Hokka-Zakrisson, Fahad Zadjali, Akihiko Yoshimura, Mikael Karlsson, Berit Carow, Martin E. Rottenberg

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The suppressor of cytokine signaling 3 (SOCS3) is a major regulator of immune responses and inflammation as it negatively regulates cytokine signaling. Here, the role of SOCS3 in thymic T cell formation was studied in Socs3fl/fl Actin-creER mice (Δsocs3) with a tamoxifen inducible and ubiquitous Socs3 deficiency. Δsocs3 thymi showed a 90% loss of cellularity and altered cortico-medullary organization. Thymocyte differentiation and proliferation was impaired at the early double negative (CD4-CD8-) cell stage and apoptosis was increased during the double positive (CD4+CD8+) cell stage, resulting in the reduction of recent thymic emigrants in peripheral organs. Using bone marrow chimeras, transplanting thymic organoids and using mice deficient of SOCS3 in thymocytes we found that expression in thymic stromal cells rather than in thymocytes was critical for T cell development. We found that SOCS3 in thymic epithelial cells (TECs) binds to the E3 ubiquitin ligase TRIM 21 and that Trim21−/− mice showed increased thymic cellularity. Δsocs3 TECs showed alterations in the expression of genes involved in positive and negative selection and lympho-stromal interactions. SOCS3-dependent signal inhibition of the common gp130 subunit of the IL-6 receptor family was redundant for T cell formation. Together, SOCS3 expression in thymic stroma cells is critical for T cell development and for maintenance of thymus architecture.

Original languageEnglish
Article number642173
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 2021 Mar 18

Keywords

  • SOCS3
  • T cells
  • TRIM21
  • thymic epithelial cell
  • thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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