PMID- 25627579 OWN - NLM STAT- MEDLINE DCOM- 20150803 LR - 20150508 IS - 1521-4141 (Electronic) IS - 0014-2980 (Linking) VI - 45 IP - 5 DP - 2015 May TI - Thymocyte-derived BDNF influences T-cell maturation at the DN3/DN4 transition stage. PG - 1326-38 LID - 10.1002/eji.201444985 [doi] AB - 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-beta 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. CI - (c) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Linker, Ralf A AU - Linker RA AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. AD - Department of Neurology, Friedrich-Alexander University Erlangen, Erlangen, Germany. FAU - Lee, De-Hyung AU - Lee DH AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. AD - Department of Neurology, Friedrich-Alexander University Erlangen, Erlangen, Germany. FAU - Flach, Anne-Christine AU - Flach AC AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. FAU - Litke, Tanja AU - Litke T AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. FAU - van den Brandt, Jens AU - van den Brandt J AD - Institute for Cellular and Molecular Immunology, University of Gottingen, Medical School, Gottingen, Germany. FAU - Reichardt, Holger M AU - Reichardt HM AD - Institute for Cellular and Molecular Immunology, University of Gottingen, Medical School, Gottingen, Germany. FAU - Lingner, Thomas AU - Lingner T AD - DNA Microarray and Deep-Sequencing Facility, Department of Developmental Biochemistry, University Medical Center Gottingen, Gottingen, Germany. FAU - Bommhardt, Ursula AU - Bommhardt U AD - Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-Guericke University, Magdeburg, Germany. FAU - Sendtner, Michael AU - Sendtner M AD - Institute for Clinical Neurobiology, University Hospital, University of Wurzburg, Wurzburg, Germany. FAU - Gold, Ralf AU - Gold R AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. AD - Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Flugel, Alexander AU - Flugel A AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. FAU - Luhder, Fred AU - Luhder F AD - Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University of Gottingen Medical School, Gottingen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150219 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/deficiency/genetics/*metabolism MH - Cell Differentiation MH - Female MH - Immunologic Memory MH - Lymphoid Tissue/cytology/immunology/metabolism MH - Lymphopoiesis MH - MAP Kinase Signaling System MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Signal Transduction MH - T-Lymphocyte Subsets/cytology/immunology/metabolism MH - T-Lymphocytes/*cytology/immunology/*metabolism OTO - NOTNLM OT - BDNF ⋅ Neurotrophins ⋅ T cells ⋅ Thymus development EDAT- 2015/01/30 06:00 MHDA- 2015/08/04 06:00 CRDT- 2015/01/29 06:00 PHST- 2014/07/02 00:00 [received] PHST- 2014/12/18 00:00 [revised] PHST- 2015/01/22 00:00 [accepted] PHST- 2015/01/29 06:00 [entrez] PHST- 2015/01/30 06:00 [pubmed] PHST- 2015/08/04 06:00 [medline] AID - 10.1002/eji.201444985 [doi] PST - ppublish SO - Eur J Immunol. 2015 May;45(5):1326-38. doi: 10.1002/eji.201444985. Epub 2015 Feb 19.