PUBLICATION
Analysis of Potential Non-Canonical or Alternate STAT5 Functions in Immune Development and Growth
- Authors
- Awasthi, N., Ward, A.C., Liongue, C.
- ID
- ZDB-PUB-230904-64
- Date
- 2023
- Source
- Frontiers in bioscience (Landmark edition) 28: 187187 (Journal)
- Registered Authors
- Liongue, Clifford, Ward, Alister C.
- Keywords
- JAK-STAT, STAT5, cytokine, growth, immunity, non-canonical
- MeSH Terms
-
- Animals
- CD3 Complex
- Longevity
- Obesity
- STAT5 Transcription Factor*/genetics
- Zebrafish*/genetics
- PubMed
- 37664942 Full text @ Front Biosci (Landmark Ed)
Citation
Awasthi, N., Ward, A.C., Liongue, C. (2023) Analysis of Potential Non-Canonical or Alternate STAT5 Functions in Immune Development and Growth. Frontiers in bioscience (Landmark edition). 28:187187.
Abstract
Background Signal transducer and activator of transcription (STAT) proteins play key roles in development, growth, and homeostasis. These roles have principally been assigned to their "canonical" function as inducible transcriptional activators acting downstream of cytokines and other factors. However, variant "non-canonical" functions have also been identified. The potential in vivo role for non-canonical STAT functions was investigated in the zebrafish model.
Methods Two zebrafish Stat5.1 mutants were generated using CRISPR/Cas9 that should impact canonical functionality: one with a deleted transactivation domain (ΔTAD) and another with a disrupted tyrosine motif (ΔTM). Immune cell development, growth, and adiposity of these Stat5.1 mutants were assessed in comparison to a Stat5.1 knockout (KO) mutant in which both canonical and non-canonical functions were ablated.
Results Both the ΔTAD and ΔTM mutants showed significantly reduced embryonic T lymphopoiesis, similar to the KO mutant. Additionally, adult ΔTAD and ΔTM mutants displayed a decrease in T cell markers in the kidney, but not as severe as the KO, which also showed T cell disruption in the spleen. Severe growth deficiency and increased adiposity were observed in all mutants, but ΔTAD showed a more modest growth defect whereas ΔTM exhibited more profound impacts on both growth and adiposity, suggesting additional gain-of-function activity.
Conclusions These results indicate that canonical Stat5.1 plays a major role in T cell development and growth throughout the lifespan and non-canonical Stat5.1 functions also contribute to aspects of adult T lymphocyte development and growth, with alternate functions impacting growth and adiposity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping