SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development
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 mice (Δ with a tamoxifen inducible and ubiquitous deficiency. Δ thymi showed a 90%...
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Published in | Frontiers in immunology Vol. 12; p. 642173 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
18.03.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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
mice (Δ
with a tamoxifen inducible and ubiquitous
deficiency. Δ
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
mice showed increased thymic cellularity. Δ
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Marita Bosticardo, National Institute of Allergy and Infectious Diseases (NIH), United States Reviewed by: Konstantina Alexandropoulos, Icahn School of Medicine at Mount Sinai, United States; Laijun Lai, University of Connecticut, United States This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2021.642173 |