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Thymocyte-derived BDNF influences T-cell maturation at the DN3/DN4 transition stage.

Authors :
Linker, Ralf A.
Lee, De‐Hyung
Flach, Anne‐Christine
Litke, Tanja
den Brandt, Jens
Reichardt, Holger M.
Lingner, Thomas
Bommhardt, Ursula
Sendtner, Michael
Gold, Ralf
Flügel, Alexander
Lühder, Fred
Source :
European Journal of Immunology; May2015, Vol. 45 Issue 5, p1326-1338, 13p
Publication Year :
2015

Abstract

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival, regeneration, and plasticity. Emerging evidence also indicates an essential role for BDNF outside the nervous system, for instance in immune cells. We therefore investigated the impact of BDNF on T cells using BDNF knockout (KO) mice and conditional KO mice lacking BDNF specifically in this lymphoid subset. In both settings, we observed diminished T-cell cellularity in peripheral lymphoid organs and an increase in CD4<superscript>+</superscript>CD44<superscript>+</superscript> memory T cells. Analysis of thymocyte development revealed diminished total thymocyte numbers, accompanied by a significant increase in CD4/CD8 double-negative (DN) thymocytes due to a partial block in the transition from the DN3 to the DN4 stage. This was neither due to increased thymocyte apoptosis nor defects in the expression of the TCR-β chain or the pre-TCR. In contrast, pERK but not pAKT levels were diminished in DN3 BDNF-deficient thymocytes. BDNF deficiency in T cells did not result in gross deficits in peripheral acute immune responses nor in changes of the homeostatic proliferation of peripheral T cells. Taken together, our data reveal a critical autocrine and/or paracrine role of T-cell-derived BDNF in thymocyte maturation involving ERK-mediated TCR signaling pathways. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00142980
Volume :
45
Issue :
5
Database :
Complementary Index
Journal :
European Journal of Immunology
Publication Type :
Academic Journal
Accession number :
102498650
Full Text :
https://doi.org/10.1002/eji.201444985