LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.

The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature α/β T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thym...

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Autores principales:	Marouan Zarrouk, Julia Rolf, Doreen Ann Cantrell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a1df02b4d2f424dbe550c009ce3c3a9
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spelling	oai:doaj.org-article:4a1df02b4d2f424dbe550c009ce3c3a92021-11-18T07:52:12ZLKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.1932-620310.1371/journal.pone.0060217https://doaj.org/article/4a1df02b4d2f424dbe550c009ce3c3a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533675/?tool=EBIhttps://doaj.org/toc/1932-6203The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature α/β T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant Vα14 NKT cells and innate TCR αβ gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase (AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.Marouan ZarroukJulia RolfDoreen Ann CantrellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e60217 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marouan Zarrouk Julia Rolf Doreen Ann Cantrell LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.
description	The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature α/β T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant Vα14 NKT cells and innate TCR αβ gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase (AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.
format	article
author	Marouan Zarrouk Julia Rolf Doreen Ann Cantrell
author_facet	Marouan Zarrouk Julia Rolf Doreen Ann Cantrell
author_sort	Marouan Zarrouk
title	LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.
title_short	LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.
title_full	LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.
title_fullStr	LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.
title_full_unstemmed	LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.
title_sort	lkb1 mediates the development of conventional and innate t cells via amp-dependent kinase autonomous pathways.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4a1df02b4d2f424dbe550c009ce3c3a9
work_keys_str_mv	AT marouanzarrouk lkb1mediatesthedevelopmentofconventionalandinnatetcellsviaampdependentkinaseautonomouspathways AT juliarolf lkb1mediatesthedevelopmentofconventionalandinnatetcellsviaampdependentkinaseautonomouspathways AT doreenanncantrell lkb1mediatesthedevelopmentofconventionalandinnatetcellsviaampdependentkinaseautonomouspathways
_version_	1718422847796281344

LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.

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