PMID- 30809231 OWN - NLM STAT- MEDLINE DCOM- 20201027 LR - 20210121 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells. PG - 222 LID - 10.3389/fimmu.2019.00222 [doi] LID - 222 AB - Apoptotic cell death of Dendritic cells (DCs) is critical for immune homeostasis. Although intrinsic mechanisms controlling DC death have not been fully characterized up to now, experimentally enforced inhibition of DC-death causes various autoimmune diseases in model systems. We have generated mice deficient for Protein Phosphatase with EF-Hands 2 (Ppef2), which is selectively expressed in CD8(+) DCs, but not in other related DC subtypes such as tissue CD103(+) DCs. Ppef2 is down-regulated rapidly upon maturation of DCs by toll-like receptor stimuli, but not upon triggering of CD40. Ppef2-deficient CD8(+) DCs accumulate the pro-apoptotic Bcl-2-like protein 11 (Bim) and show increased apoptosis and reduced competitve repopulation capacities. Furthermore, Ppef2(-/-) CD8(+) DCs have strongly diminished antigen presentation capacities in vivo, as CD8(+) T cells primed by Ppef2(-/-) CD8(+) DCs undergo reduced expansion. In conclusion, our data suggests that Ppef2 is crucial to support survival of immature CD8(+) DCs, while Ppef2 down-regulation during DC-maturation limits T cell responses. FAU - Zwick, Markus AU - Zwick M AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. FAU - Ulas, Thomas AU - Ulas T AD - Life and Medical Sciences Institute, Bonn, Germany. FAU - Cho, Yi-Li AU - Cho YL AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. FAU - Ried, Christine AU - Ried C AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. FAU - Grosse, Leonie AU - Grosse L AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. FAU - Simon, Charlotte AU - Simon C AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. FAU - Bernhard, Caroline AU - Bernhard C AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. FAU - Busch, Dirk H AU - Busch DH AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. FAU - Schultze, Joachim L AU - Schultze JL AD - Life and Medical Sciences Institute, Bonn, Germany. AD - PRECISE-Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn, Bonn, Germany. FAU - Buchholz, Veit R AU - Buchholz VR AD - Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany. FAU - Stutte, Susanne AU - Stutte S AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. FAU - Brocker, Thomas AU - Brocker T AD - Faculty of Medicine, Biomedical Center (BMC), Institute for Immunology, LMU Munich, Planegg-Martinsried, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190212 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Bcl-2-Like Protein 11) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.16 (Ppef2 protein, mouse) SB - IM MH - Animals MH - Antigen Presentation MH - Apoptosis MH - Bcl-2-Like Protein 11/genetics/metabolism MH - CD8-Positive T-Lymphocytes/*immunology MH - Cell Differentiation MH - Cell Proliferation MH - Cells, Cultured MH - Cross-Priming MH - Dendritic Cells/*immunology MH - Homeostasis MH - Lymphocyte Activation MH - Mice MH - Mice, Knockout MH - Phosphoprotein Phosphatases/genetics/*metabolism PMC - PMC6379467 OTO - NOTNLM OT - CD8 T cell priming OT - DC-maturation OT - apoptosis OT - cross-presentation OT - dendritic cells OT - immune homeostasis EDAT- 2019/02/28 06:00 MHDA- 2020/10/28 06:00 PMCR- 2019/01/01 CRDT- 2019/02/28 06:00 PHST- 2018/09/18 00:00 [received] PHST- 2019/01/25 00:00 [accepted] PHST- 2019/02/28 06:00 [entrez] PHST- 2019/02/28 06:00 [pubmed] PHST- 2020/10/28 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.00222 [doi] PST - epublish SO - Front Immunol. 2019 Feb 12;10:222. doi: 10.3389/fimmu.2019.00222. eCollection 2019.