title: Thymocyte-derived BDNF influences T-cell maturation at the DN3/DN4 transition stage.
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(+) CD44(+) 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.
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.|Department of Neurology, Friedrich-Alexander University Erlangen, Erlangen, Germany.
authors: Ralf A
authors: RA
authors: Linker
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.|Department of Neurology, Friedrich-Alexander University Erlangen, Erlangen, Germany.
authors: De-Hyung
authors: DH
authors: Lee
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.
authors: Anne-Christine
authors: AC
authors: Flach
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.
authors: Tanja
authors: T
authors: Litke
authors: Institute for Cellular and Molecular Immunology, University of Göttingen, Medical School, Göttingen, Germany.
authors: Jens
authors: J
authors: van den Brandt
authors: Institute for Cellular and Molecular Immunology, University of Göttingen, Medical School, Göttingen, Germany.
authors: Holger M
authors: HM
authors: Reichardt
authors: DNA Microarray and Deep-Sequencing Facility, Department of Developmental Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors: Thomas
authors: T
authors: Lingner
authors: Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-Guericke University, Magdeburg, Germany.
authors: Ursula
authors: U
authors: Bommhardt
authors: Institute for Clinical Neurobiology, University Hospital, University of Würzburg, Würzburg, Germany.
authors: Michael
authors: M
authors: Sendtner
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.|Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors: Ralf
authors: R
authors: Gold
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.
authors: Alexander
authors: A
authors: Flügel
authors: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Göttingen Medical School, Göttingen, Germany.
authors: Fred
authors: F
authors: Lühder
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D007156:Immunologic Memory; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF ⋅ Neurotrophins ⋅ T cells ⋅ Thymus development