Deletion of nemo-like kinase in T cells reduces single-positive CD8+thymocyte population
(2020) In Journal of Immunology 205(7). p.1830-1841- Abstract
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... (More)
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.
(Less)
- author
- Daams, Renée LU ; Sime, Wondossen LU ; Leandersson, Karin LU ; Sitnicka, Ewa LU and Massoumi, Ramin LU
- organization
-
- Molecular Tumor Pathology (research group)
- LUCC: Lund University Cancer Centre
- Cancer Immunology, Malmö (research group)
- Lymphoid Development and Regulation (research group)
- Division of Molecular Hematology (DMH)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Division of Translational Cancer Research
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 205
- issue
- 7
- pages
- 12 pages
- publisher
- American Association of Immunologists
- external identifiers
-
- pmid:32839237
- scopus:85091469816
- ISSN
- 0022-1767
- DOI
- 10.4049/jimmunol.2000109
- language
- English
- LU publication?
- yes
- id
- d8e7444b-9426-4159-b5ac-9abc907a4d11
- date added to LUP
- 2020-10-23 12:52:02
- date last changed
- 2024-07-25 03:10:56
@article{d8e7444b-9426-4159-b5ac-9abc907a4d11, abstract = {{<p>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. </p>}}, author = {{Daams, Renée and Sime, Wondossen and Leandersson, Karin and Sitnicka, Ewa and Massoumi, Ramin}}, issn = {{0022-1767}}, language = {{eng}}, number = {{7}}, pages = {{1830--1841}}, publisher = {{American Association of Immunologists}}, series = {{Journal of Immunology}}, title = {{Deletion of nemo-like kinase in T cells reduces single-positive CD8<sup>+</sup>thymocyte population}}, url = {{http://dx.doi.org/10.4049/jimmunol.2000109}}, doi = {{10.4049/jimmunol.2000109}}, volume = {{205}}, year = {{2020}}, }