Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis

PloS One
Julia BischofRobert Jaster

Abstract

The mouse strain MRL/MpJ is prone to spontaneously develop autoimmune pancreatitis (AIP). To elucidate the genetic control towards the development of the phenotype and to characterize contributions of immunocompetent cell types, MRL/MpJ mice were interbred with three additional strains (BXD2/TYJ, NZM2410/J, CAST/EIJ) for four generations in an advanced intercross line. Cellular phenotypes were determined by flow cytometric quantification of splenic leukocytes and complemented by the histopathological evaluation of pancreatic lesions. An Illumina SNP array was used for genotyping. QTL analyses were performed with the R implementation of HAPPY. Out of 41 leukocyte subpopulations (B cells, T cells and dendritic cells), only three were significantly associated with AIP: While CD4+/CD44high memory T cells and CD4+/CD69+ T helper (Th) cells correlated positively with the disease, the cytotoxic T cell phenotype CD8+/CD44low showed a negative correlation. A QTL for AIP on chromosome 2 overlapped with QTLs for CD4+/CD44high and CD8+/CD44high memory T cells, FoxP3+/CD4+ and FoxP3+/CD8+ regulatory T cells (Tregs), and CD8+/CD69+ cytotoxic T cells. On chromosome 6, overlapping QTLs for AIP and CD4+/IL17+ Th17 cells and again FoxP3+/CD8+ Tr...Continue Reading

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Citations

Jan 23, 2016·Veterinary Parasitology·ZhenChao ZhangXiangRui Li
Feb 1, 2018·Journal of Cellular and Molecular Medicine·Luise EhlersRobert Jaster
Jul 10, 2020·Journal of Cellular and Molecular Medicine·Robert JasterSaleh M Ibrahim
Oct 28, 2016·The Journal of Eukaryotic Microbiology·ZhenChao ZhangXiangRui Li

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Methods Mentioned

BETA
light microscopy
Flow Cytometry
FACS
genotyping

Software Mentioned

R
R package of HAPPY
BD CellQuest
Debian Linux

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