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

First Author  Zarrouk M Year  2013
Journal  PLoS One Volume  8
Issue  3 Pages  e60217
PubMed ID  23533675 Mgi Jnum  J:346638
Mgi Id  MGI:6233361 Doi  10.1371/journal.pone.0060217
Citation  Zarrouk M, et al. (2013) LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways. PLoS One 8(3):e60217
abstractText  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 alpha/beta 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 Valpha14 NKT cells and innate TCR alphabeta 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.
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