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

Autor: Saleh Yazdani, Gerda A. Noordmans, Harry van Goor, Jan-Luuk Hillebrands, Yuan Huang, Christina R. Caputo, Ron Korstanje, Luiz Henrique Monteiro, Jaap van den Born, Peter Heeringa
Přispěvatelé: Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT)
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Candidate gene
Pathology
Aging
Physiology
lcsh:Medicine
Kidney
DISEASE
Mice
Chronic Kidney Disease
Genetics of the Immune System
Medicine and Health Sciences
IMMUNE-RESPONSE
lcsh:Science
Multidisciplinary
Intracellular Signaling Peptides and Proteins
HUMAN KIDNEY
Animal Models
Immunohistochemistry
FAMILY
Lymphatic system
medicine.anatomical_structure
Phenotype
Liver
Nephrology
Female
Lymph
Research Article
EXPRESSION
medicine.medical_specialty
Lymphoid Tissue
High endothelial venules
Immunology
Ki-1 Antigen
Mouse Models
Immunopathology
Biology
Research and Analysis Methods
Polymorphism
Single Nucleotide
Immune system
Model Organisms
Sex Factors
NEOGENESIS
medicine
Animals
Genetic Association Studies
Adaptor Proteins
Signal Transducing
Lymphatic Vessels
lcsh:R
CHRONIC REJECTION
Immunity
Kidney metabolism
Biology and Life Sciences
ENDOTHELIAL-CELLS
TISSUE
Tubulointerstitial Disease
CD30
lcsh:Q
Clinical Immunology
Physiological Processes
Organism Development
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, 9(3):e91850. PUBLIC LIBRARY SCIENCE
PLoS ONE, Vol 9, Iss 3, p e91850 (2014)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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