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Updated: Nov 10, 2025

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

Yu Gao1, Ruining Liu1, Chenfei He1

  • 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Frontiers in Immunology
|April 5, 2021
PubMed
Summary

Suppressor of cytokine signaling 3 (SOCS3) is crucial for T cell development. SOCS3 in thymic stromal cells, not T cells, maintains thymus architecture and promotes T cell formation.

Keywords:
SOCS3T cellsTRIM21thymic epithelial cellthymus

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Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • Suppressor of cytokine signaling 3 (SOCS3) negatively regulates cytokine signaling, impacting immune responses and inflammation.
  • The precise role of SOCS3 in thymic T cell development and thymus organogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the function of SOCS3 in T cell development within the thymus.
  • To determine whether SOCS3 expression in thymocytes or thymic stromal cells is critical for T cell formation.

Main Methods:

  • Utilized tamoxifen-inducible, ubiquitous Socs3-deficient mice (Δsocs3) to study SOCS3's role.
  • Employed bone marrow chimeras, thymic organoid transplantation, and cell-specific SOCS3 deficiency models.
  • Analyzed thymocyte differentiation, proliferation, apoptosis, and gene expression in thymic epithelial cells (TECs).

Main Results:

  • Δsocs3 mice exhibited a 90% loss in thymic cellularity and disrupted cortico-medullary organization.
  • Thymocyte development was impaired at the double-negative stage, with increased apoptosis at the double-positive stage.
  • SOCS3 expression in thymic stromal cells, particularly TECs, was essential for T cell development, whereas SOCS3 in thymocytes was not.
  • SOCS3 in TECs interacts with TRIM21, and Trim21 deficiency led to increased thymic cellularity.

Conclusions:

  • SOCS3 expression in thymic stromal cells is critical for T cell development and maintaining thymus architecture.
  • SOCS3's role in TECs is vital for regulating gene expression involved in thymocyte selection and lympho-stromal interactions.
  • The inhibitory function of SOCS3 on the gp130 subunit of the IL-6 receptor family is not essential for T cell formation.