Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.

The immune system and iron availability are intimately linked as appropriate iron supply is needed for cell proliferation, while excess iron, as observed in hemochromatosis, may reduce subsets of lymphocytes. We have tested the effects of a ferritin H gene deletion on lymphocytes. Mx-Cre mediated co...

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Autores principales:	Liviu Vanoaica, Larry Richman, Maike Jaworski, Deepak Darshan, Sanjiv A Luther, Lukas C Kühn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba2833c096394994b75356945d848b06
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spelling	oai:doaj.org-article:ba2833c096394994b75356945d848b062021-11-18T08:31:32ZConditional deletion of ferritin h in mice reduces B and T lymphocyte populations.1932-620310.1371/journal.pone.0089270https://doaj.org/article/ba2833c096394994b75356945d848b062014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586648/?tool=EBIhttps://doaj.org/toc/1932-6203The immune system and iron availability are intimately linked as appropriate iron supply is needed for cell proliferation, while excess iron, as observed in hemochromatosis, may reduce subsets of lymphocytes. We have tested the effects of a ferritin H gene deletion on lymphocytes. Mx-Cre mediated conditional deletion of ferritin H in bone marrow reduced the number of mature B cells and peripheral T cells in all lymphoid organs. FACS analysis showed an increase in the labile iron pool, enhanced reactive oxygen species formation and mitochondrial depolarization. The findings were confirmed by a B-cell specific deletion using Fth(lox/lox) ; CD19-Cre mice. Mature B cells were strongly under-represented in bone marrow and spleen of the deleted mice, whereas pre-B and immature B cells were not affected. Bone marrow B cells showed increased proliferation as judged by the number of cells in S and G2/M phase as well as BrdU incorporation. Upon in vitro culture with B-cell activating factor of the tumor necrosis factor family (BAFF), ferritin H-deleted spleen B cells showed lower survival rates than wild type cells. This was partially reversed with iron-chelator deferiprone. The loss of T cells was also confirmed by a T cell-specific deletion in Fth(lox/lox) ;CD4-Cre mice. Our data show that ferritin H is required for B and T cell survival by actively reducing the labile iron pool. They further suggest that natural B and T cell maturation is influenced by intracellular iron levels and possibly deregulated in iron excess or deprivation.Liviu VanoaicaLarry RichmanMaike JaworskiDeepak DarshanSanjiv A LutherLukas C KühnPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89270 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liviu Vanoaica Larry Richman Maike Jaworski Deepak Darshan Sanjiv A Luther Lukas C Kühn Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.
description	The immune system and iron availability are intimately linked as appropriate iron supply is needed for cell proliferation, while excess iron, as observed in hemochromatosis, may reduce subsets of lymphocytes. We have tested the effects of a ferritin H gene deletion on lymphocytes. Mx-Cre mediated conditional deletion of ferritin H in bone marrow reduced the number of mature B cells and peripheral T cells in all lymphoid organs. FACS analysis showed an increase in the labile iron pool, enhanced reactive oxygen species formation and mitochondrial depolarization. The findings were confirmed by a B-cell specific deletion using Fth(lox/lox) ; CD19-Cre mice. Mature B cells were strongly under-represented in bone marrow and spleen of the deleted mice, whereas pre-B and immature B cells were not affected. Bone marrow B cells showed increased proliferation as judged by the number of cells in S and G2/M phase as well as BrdU incorporation. Upon in vitro culture with B-cell activating factor of the tumor necrosis factor family (BAFF), ferritin H-deleted spleen B cells showed lower survival rates than wild type cells. This was partially reversed with iron-chelator deferiprone. The loss of T cells was also confirmed by a T cell-specific deletion in Fth(lox/lox) ;CD4-Cre mice. Our data show that ferritin H is required for B and T cell survival by actively reducing the labile iron pool. They further suggest that natural B and T cell maturation is influenced by intracellular iron levels and possibly deregulated in iron excess or deprivation.
format	article
author	Liviu Vanoaica Larry Richman Maike Jaworski Deepak Darshan Sanjiv A Luther Lukas C Kühn
author_facet	Liviu Vanoaica Larry Richman Maike Jaworski Deepak Darshan Sanjiv A Luther Lukas C Kühn
author_sort	Liviu Vanoaica
title	Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.
title_short	Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.
title_full	Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.
title_fullStr	Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.
title_full_unstemmed	Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.
title_sort	conditional deletion of ferritin h in mice reduces b and t lymphocyte populations.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ba2833c096394994b75356945d848b06
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Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations.

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