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Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice

A hallmark of aging-related organ deterioration is a dysregulated immune response characterized by pathologic leukocyte infiltration of affected tissues. Mechanisms and genes involved are as yet unknown. To identify genes associated with aging-related renal infiltration, we analyzed kidneys from age...

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Autores principales: Huang, Yuan, Caputo, Christina R., Noordmans, Gerda A., Yazdani, Saleh, Monteiro, Luiz Henrique, van den Born, Jaap, van Goor, Harry, Heeringa, Peter, Korstanje, Ron, Hillebrands, Jan-Luuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956762/
https://www.ncbi.nlm.nih.gov/pubmed/24637805
http://dx.doi.org/10.1371/journal.pone.0091850
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author Huang, Yuan
Caputo, Christina R.
Noordmans, Gerda A.
Yazdani, Saleh
Monteiro, Luiz Henrique
van den Born, Jaap
van Goor, Harry
Heeringa, Peter
Korstanje, Ron
Hillebrands, Jan-Luuk
author_facet Huang, Yuan
Caputo, Christina R.
Noordmans, Gerda A.
Yazdani, Saleh
Monteiro, Luiz Henrique
van den Born, Jaap
van Goor, Harry
Heeringa, Peter
Korstanje, Ron
Hillebrands, Jan-Luuk
author_sort Huang, Yuan
collection PubMed
description A hallmark of aging-related organ deterioration is a dysregulated immune response characterized by pathologic leukocyte infiltration of affected tissues. Mechanisms and genes involved are as yet unknown. To identify genes associated with aging-related renal infiltration, we analyzed kidneys from aged mice (≥20 strains) for infiltrating leukocytes followed by Haplotype Association Mapping (HAM) analysis. Immunohistochemistry revealed CD45(+) cell clusters (predominantly T and B cells) in perivascular areas coinciding with PNAd(+) high endothelial venules and podoplanin(+) lymph vessels indicative of tertiary lymphoid organs. Cumulative cluster size increased with age (analyzed at 6, 12 and 20 months). Based on the presence or absence of clusters in male and female mice at 20 months, HAM analysis revealed significant associations with loci on Chr1, Chr2, Chr8 and Chr14 in male mice, and with loci on Chr4, Chr7, Chr13 and Chr14 in female mice. Wisp2 (Chr2) showed the strongest association (P = 5.00×10(−137)) in male mice; Ctnnbip1 (P = 6.42×10(−267)) and Tnfrsf8 (P = 5.42×10(−245)) (both on Chr4) showed the strongest association in female mice. Both Wisp2 and Ctnnbip1 are part of the Wnt-signaling pathway and the encoded proteins were expressed within the tertiary lymphoid organs. In conclusion, this study revealed differential lymphocytic infiltration and tertiary lymphoid organ formation in aged mouse kidneys across different inbred mouse strains. HAM analysis identified candidate genes involved in the Wnt-signaling pathway that may be causally linked to tertiary lymphoid organ formation.
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spelling pubmed-39567622014-03-18 Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice Huang, Yuan Caputo, Christina R. Noordmans, Gerda A. Yazdani, Saleh Monteiro, Luiz Henrique van den Born, Jaap van Goor, Harry Heeringa, Peter Korstanje, Ron Hillebrands, Jan-Luuk PLoS One Research Article A hallmark of aging-related organ deterioration is a dysregulated immune response characterized by pathologic leukocyte infiltration of affected tissues. Mechanisms and genes involved are as yet unknown. To identify genes associated with aging-related renal infiltration, we analyzed kidneys from aged mice (≥20 strains) for infiltrating leukocytes followed by Haplotype Association Mapping (HAM) analysis. Immunohistochemistry revealed CD45(+) cell clusters (predominantly T and B cells) in perivascular areas coinciding with PNAd(+) high endothelial venules and podoplanin(+) lymph vessels indicative of tertiary lymphoid organs. Cumulative cluster size increased with age (analyzed at 6, 12 and 20 months). Based on the presence or absence of clusters in male and female mice at 20 months, HAM analysis revealed significant associations with loci on Chr1, Chr2, Chr8 and Chr14 in male mice, and with loci on Chr4, Chr7, Chr13 and Chr14 in female mice. Wisp2 (Chr2) showed the strongest association (P = 5.00×10(−137)) in male mice; Ctnnbip1 (P = 6.42×10(−267)) and Tnfrsf8 (P = 5.42×10(−245)) (both on Chr4) showed the strongest association in female mice. Both Wisp2 and Ctnnbip1 are part of the Wnt-signaling pathway and the encoded proteins were expressed within the tertiary lymphoid organs. In conclusion, this study revealed differential lymphocytic infiltration and tertiary lymphoid organ formation in aged mouse kidneys across different inbred mouse strains. HAM analysis identified candidate genes involved in the Wnt-signaling pathway that may be causally linked to tertiary lymphoid organ formation. Public Library of Science 2014-03-17 /pmc/articles/PMC3956762/ /pubmed/24637805 http://dx.doi.org/10.1371/journal.pone.0091850 Text en © 2014 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Huang, Yuan
Caputo, Christina R.
Noordmans, Gerda A.
Yazdani, Saleh
Monteiro, Luiz Henrique
van den Born, Jaap
van Goor, Harry
Heeringa, Peter
Korstanje, Ron
Hillebrands, Jan-Luuk
Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice
title Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice
title_full Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice
title_fullStr Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice
title_full_unstemmed Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice
title_short Identification of Novel Genes Associated with Renal Tertiary Lymphoid Organ Formation in Aging Mice
title_sort identification of novel genes associated with renal tertiary lymphoid organ formation in aging mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956762/
https://www.ncbi.nlm.nih.gov/pubmed/24637805
http://dx.doi.org/10.1371/journal.pone.0091850
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