scholarly journals Suppressor of Cytokine Signaling 1 Regulates Embryonic Myelopoiesis Independently of Its Effects on T Cell Development

2011 ◽  
Vol 186 (8) ◽  
pp. 4751-4761 ◽  
Author(s):  
Lynda A. O’Sullivan ◽  
Suzita M. Noor ◽  
Monique C. Trengove ◽  
Rowena S. Lewis ◽  
Clifford Liongue ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling

Overexpression of suppressor of cytokine signaling-1 impairs pre-T-cell receptor–induced proliferation but not differentiation of immature thymocytes

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2269-2277 ◽  
Author(s):  
Sébastien Trop ◽  
Paulo De Sepulveda ◽  
Juan Carlos Zúñiga-Pflücker ◽  
Robert Rottapel
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Development ◽  
Constitutive Expression ◽  
Cell Receptor ◽  
Cell Development ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Immature Thymocytes

Abstract Cytokines play an essential role during early T-cell development. However, the mechanisms controlling cytokine signaling in developing thymocytes have not been elucidated. Cytokine receptor signaling can be modulated by suppressor of cytokine signaling-1 (SOCS-1), which acts as a negative regulator of Janus kinases. SOCS-1 is normally expressed throughout thymocyte development; however, retroviral-mediated overexpression of SOCS-1 in fetal liver–derived hematopoietic progenitors prevented their progression beyond the earliest stage of T-cell development. Further analysis revealed that SOCS-1 expression is transiently suppressed following pre-T-cell receptor (TCR) signaling. Moreover, constitutive expression of SOCS-1 abrogated pre-TCR– mediated expansion of immature thymocytes but did not interfere with differentiation. These findings reveal that SOCS-1 serves to regulate cytokine signaling at critical checkpoints during early T-cell development.

scholarly journals Evolutionary transition from degenerate to nonredundant cytokine signaling networks supporting intrathymic T cell development

2019 ◽  
Vol 116 (52) ◽  
pp. 26759-26767
Author(s):  
Divine-Fondzenyuy Lawir ◽  
Isabell Hess ◽  
Katarzyna Sikora ◽  
Norimasa Iwanami ◽  
Iliana Siamishi ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
Genetic Interaction ◽  
Expression Patterns ◽  
T Cell Development ◽  
Cell Development ◽  
Cytokine Signaling ◽  
Cytokine Network ◽  
Immune Disorder ◽  
Mild Reduction

In mammals, T cell development critically depends on the IL-7 cytokine signaling pathway. Here we describe the identification of the zebrafish ortholog of mammalian IL-7 based on chromosomal localization, deduced protein sequence, and expression patterns. To examine the biological role ofil7in teleosts, we generated anil7allele lacking most of its coding exons using CRISPR/Cas9-based mutagenesis.il7-deficient animals are viable and exhibit no obvious signs of immune disorder. With respect to intrathymic T cell development,il7deficiency is associated with only a mild reduction of thymocyte numbers, contrasting with a more pronounced impairment of T cell development inil7r-deficient fish. Genetic interaction studies betweenil7andil7rmutants, andil7andcrlf2(tslpr) mutants suggest the contribution of additional, as-yet unidentified cytokines to intrathymic T cell development. Such activities were also ascertained for other cytokines, such as il2 and il15, collectively indicating that in contrast to the situation in mammals, T cell development in the thymus of teleosts is driven by a degenerate multicomponent network of γccytokines; this explains why deficiencies of single components have little detrimental effect. In contrast, the dependence on a single cytokine in the mammalian thymus has catastrophic consequences in cases of congenital deficiencies in genes affecting the IL-7 signaling pathway. We speculate that the transition from a degenerate to a nonredundant cytokine network supporting intrathymic T cell development emerged as a consequence of repurposing evolutionarily ancient constitutive cytokine pathways for regulatory functions in the mammalian peripheral immune system.

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Gao ◽  
Ruining Liu ◽  
Chenfei He ◽  
Juan Basile ◽  
Mattias Vesterlund ◽  
...  
Keyword(s):  
T Cell ◽  
Stromal Cells ◽  
T Cell Development ◽  
Cell Formation ◽  
Cell Development ◽  
Cytokine Signaling ◽  
Cell Stage ◽  
Socs3 Expression ◽  
Cd8 Cell ◽  
Thymic Stromal Cells

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/flActin-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.

Differential Roles of Cytokine Signaling during T-cell Development

1999 ◽  
Vol 64 (0) ◽  
pp. 389-396 ◽  
Author(s):  
R. MORIGGL ◽  
J.-C. MARINE ◽  
D.J. TOPHAM ◽  
S. TEGLUND ◽  
V. SEXL ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Cytokine Signaling

scholarly journals TGF-β Cytokine Signaling Promotes CD8+ T Cell Development and Low-Affinity CD4+ T Cell Homeostasis by Regulation of Interleukin-7 Receptor α Expression

Immunity ◽  
2013 ◽  
Vol 39 (2) ◽  
pp. 335-346 ◽  
Author(s):  
Weiming Ouyang ◽  
Soyoung A. Oh ◽  
Qian Ma ◽  
Michael R. Bivona ◽  
Jinfang Zhu ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Cd8 T Cell ◽  
Cell Development ◽  
Cd4 T Cell ◽  
Cytokine Signaling ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Interleukin 7
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