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Deletion of nemo-like kinase in T cells reduces single-positive CD8+thymocyte population

Daams, Renée LU ; Sime, Wondossen LU ; Leandersson, Karin LU orcid ; Sitnicka, Ewa LU and Massoumi, Ramin LU (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.

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organization
publishing date
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
  • scopus:85091469816
  • pmid:32839237
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
2024-05-15 20:00:09
@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}},
}