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Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379467/ https://www.ncbi.nlm.nih.gov/pubmed/30809231 http://dx.doi.org/10.3389/fimmu.2019.00222 |
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author | Zwick, Markus Ulas, Thomas Cho, Yi-Li Ried, Christine Grosse, Leonie Simon, Charlotte Bernhard, Caroline Busch, Dirk H. Schultze, Joachim L. Buchholz, Veit R. Stutte, Susanne Brocker, Thomas |
author_facet | Zwick, Markus Ulas, Thomas Cho, Yi-Li Ried, Christine Grosse, Leonie Simon, Charlotte Bernhard, Caroline Busch, Dirk H. Schultze, Joachim L. Buchholz, Veit R. Stutte, Susanne Brocker, Thomas |
author_sort | Zwick, Markus |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6379467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63794672019-02-26 Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells Zwick, Markus Ulas, Thomas Cho, Yi-Li Ried, Christine Grosse, Leonie Simon, Charlotte Bernhard, Caroline Busch, Dirk H. Schultze, Joachim L. Buchholz, Veit R. Stutte, Susanne Brocker, Thomas Front Immunol Immunology 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. Frontiers Media S.A. 2019-02-12 /pmc/articles/PMC6379467/ /pubmed/30809231 http://dx.doi.org/10.3389/fimmu.2019.00222 Text en Copyright © 2019 Zwick, Ulas, Cho, Ried, Grosse, Simon, Bernhard, Busch, Schultze, Buchholz, Stutte and Brocker. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zwick, Markus Ulas, Thomas Cho, Yi-Li Ried, Christine Grosse, Leonie Simon, Charlotte Bernhard, Caroline Busch, Dirk H. Schultze, Joachim L. Buchholz, Veit R. Stutte, Susanne Brocker, Thomas Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells |
title | Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells |
title_full | Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells |
title_fullStr | Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells |
title_full_unstemmed | Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells |
title_short | Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8(+) Dendritic Cells |
title_sort | expression of the phosphatase ppef2 controls survival and function of cd8(+) dendritic cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379467/ https://www.ncbi.nlm.nih.gov/pubmed/30809231 http://dx.doi.org/10.3389/fimmu.2019.00222 |
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