Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice

Background - Aging is associated with a decline in lymphocyte function however, little is known about dendritic cell (DC) subsets and aging. Aging is also associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Whether age-associated increases...

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Main Authors: Gardner, Joanne, Mamotte, Cyril, McGonigle, T., Dye, Danielle, Jackaman, Connie, Nelson, Delia
Format: Journal Article
Published: BioMed Central Ltd. 2014
Subjects:
Online Access:http://www.immunityageing.com/content/11/1/11
http://hdl.handle.net/20.500.11937/45376
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author Gardner, Joanne
Mamotte, Cyril
McGonigle, T.
Dye, Danielle
Jackaman, Connie
Nelson, Delia
author_facet Gardner, Joanne
Mamotte, Cyril
McGonigle, T.
Dye, Danielle
Jackaman, Connie
Nelson, Delia
author_sort Gardner, Joanne
building Curtin Institutional Repository
collection Online Access
description Background - Aging is associated with a decline in lymphocyte function however, little is known about dendritic cell (DC) subsets and aging. Aging is also associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Whether age-associated increases in lipid levels influence DC biology is unknown. Thus, the effects of aging on DC subsets were assessed in vivo using young adult and elderly C57BL/6 J mice. Results - Major age-related changes included increased CD11c+ DC numbers in lymph nodes, spleens and livers, but not lungs, and significantly increased proportions of plasmacytoid (pDC) and CD4-CD8α+ DCs in lymph nodes and livers. Other changes included altered pDC activation status (decreased CD40, increased MHC class-I and MHC class-II), increased lipid content in pDCs and CD4-CD8α+ DCs, and increased expression of key mediators of lipid uptake including lipoprotein lipase, scavenger receptors (CD36, CD68 and LRP-1) in most tissues. Conclusions - Aging is associated with organ-specific numerical changes in DC subsets, and DC activation status, and increased lipid content in pDCs and CD4-CD8α+ DCs. Up-regulation of lipoprotein lipase and scavenger receptors by lipid-rich pDCs and CD4-CD8α+ DCs suggests these molecules contribute to DC lipid accumulation in the elderly. Lipid accumulation and modulated activation in pDCs and CD4-CD8α+ DCs may contribute to the declining responses to vaccination and infection with age.
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spelling curtin-20.500.11937-453762017-09-13T14:22:50Z Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice Gardner, Joanne Mamotte, Cyril McGonigle, T. Dye, Danielle Jackaman, Connie Nelson, Delia Immunosenescence Aged mice Dendritic cell Lipid uptake Background - Aging is associated with a decline in lymphocyte function however, little is known about dendritic cell (DC) subsets and aging. Aging is also associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Whether age-associated increases in lipid levels influence DC biology is unknown. Thus, the effects of aging on DC subsets were assessed in vivo using young adult and elderly C57BL/6 J mice. Results - Major age-related changes included increased CD11c+ DC numbers in lymph nodes, spleens and livers, but not lungs, and significantly increased proportions of plasmacytoid (pDC) and CD4-CD8α+ DCs in lymph nodes and livers. Other changes included altered pDC activation status (decreased CD40, increased MHC class-I and MHC class-II), increased lipid content in pDCs and CD4-CD8α+ DCs, and increased expression of key mediators of lipid uptake including lipoprotein lipase, scavenger receptors (CD36, CD68 and LRP-1) in most tissues. Conclusions - Aging is associated with organ-specific numerical changes in DC subsets, and DC activation status, and increased lipid content in pDCs and CD4-CD8α+ DCs. Up-regulation of lipoprotein lipase and scavenger receptors by lipid-rich pDCs and CD4-CD8α+ DCs suggests these molecules contribute to DC lipid accumulation in the elderly. Lipid accumulation and modulated activation in pDCs and CD4-CD8α+ DCs may contribute to the declining responses to vaccination and infection with age. 2014 Journal Article http://hdl.handle.net/20.500.11937/45376 10.1186/1742-4933-11-11 http://www.immunityageing.com/content/11/1/11 BioMed Central Ltd. fulltext
spellingShingle Immunosenescence
Aged mice
Dendritic cell
Lipid uptake
Gardner, Joanne
Mamotte, Cyril
McGonigle, T.
Dye, Danielle
Jackaman, Connie
Nelson, Delia
Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice
title Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice
title_full Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice
title_fullStr Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice
title_full_unstemmed Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice
title_short Lipid-laden partially-activated plasmacytoid and CD4-CD8a+ dendritic cells accumulate in tissues in elderly mice
title_sort lipid-laden partially-activated plasmacytoid and cd4-cd8a+ dendritic cells accumulate in tissues in elderly mice
topic Immunosenescence
Aged mice
Dendritic cell
Lipid uptake
url http://www.immunityageing.com/content/11/1/11
http://hdl.handle.net/20.500.11937/45376