Deletion of Nemo-like Kinase in T Cells Reduces Single-Positive CD8+ Thymocyte Population
| Autor: | Wondossen Sime, Karin Leandersson, Renée Daams, Ramin Massoumi, Ewa Sitnicka |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
education.field_of_study
Kinase T cell Cellular differentiation Immunology Population Wnt signaling pathway Biology Cell biology 03 medical and health sciences Thymocyte 0302 clinical medicine medicine.anatomical_structure medicine Immunology and Allergy Signal transduction education CD8 030215 immunology |
| Zdroj: | The Journal of Immunology. 205:1830-1841 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The β-catenin/Wnt signaling pathway plays an important role in all stages of T cell development. Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine kinase and a negative regulator of the Wnt signaling pathway. NLK can directly phosphorylate histone deacetylase 1 (HDAC1), as well as T cell factor/lymphoid enhancer–binding factor (TCF/LEF), causing subsequent repression of target gene transcription. By engineering mice lacking NLK in early stages of T cell development, we set out to characterize the role NLK plays in T cell development and found that deletion of NLK does not affect mouse health or lymphoid tissue development. Instead, these mice harbored a reduced number of single-positive (SP) CD8+ thymocytes without any defects in the SP CD4+ thymocyte population. The decrease in SP CD8+ thymocytes was not caused by a block in differentiation from double-positive CD4+CD8+ cells. Neither TCR signaling nor activation was altered in the absence of NLK. Instead, we observed a significant increase in cell death and reduced phosphorylation of LEF1 as well as HDAC1 among NLK-deleted SP CD8+ cells. Thus, NLK seems to play an important role in the survival of CD8+ thymocytes. Our data provide evidence for a new function for NLK with regard to its involvement in T cell development and supporting survival of SP CD8+ thymocytes. |
| Databáze: | OpenAIRE |
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