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

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Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis. / Bischof, Julia; Müller, Sarah; Borufka, Luise; Asghari, Farahnaz; Möller, Steffen; Holzhüter, Stephanie-Anna; Nizze, Horst; Ibrahim, Saleh M; Jaster, Robert.

In: PLOS ONE, Vol. 10, No. 9, 2015, p. e0136298.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bischof, J, Müller, S, Borufka, L, Asghari, F, Möller, S, Holzhüter, S-A, Nizze, H, Ibrahim, SM & Jaster, R 2015, 'Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis', PLOS ONE, vol. 10, no. 9, pp. e0136298. https://doi.org/10.1371/journal.pone.0136298

APA

Bischof, J., Müller, S., Borufka, L., Asghari, F., Möller, S., Holzhüter, S-A., Nizze, H., Ibrahim, S. M., & Jaster, R. (2015). Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis. PLOS ONE, 10(9), e0136298. https://doi.org/10.1371/journal.pone.0136298

Vancouver

Bischof J, Müller S, Borufka L, Asghari F, Möller S, Holzhüter S-A et al. Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis. PLOS ONE. 2015;10(9):e0136298. https://doi.org/10.1371/journal.pone.0136298

Bibtex

@article{c5499bb76db04ccebd464742ec2e01a6,
title = "Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis",
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+ Tregs were observed. In conclusion, CD4+/CD44high memory T cells are the only leukocyte subtype that could be linked to AIP both by correlation studies and from observed overlapping QTL. The potential role of this cell type in the pathogenesis of AIP warrants further investigations.",
keywords = "Animals, Antigens, CD44, Autoimmune Diseases, CD4-Positive T-Lymphocytes, Female, Flow Cytometry, Male, Mice, Mice, Inbred Strains, Pancreas, Pancreatitis, Chronic, Quantitative Trait Loci, T-Lymphocyte Subsets",
author = "Julia Bischof and Sarah M{\"u}ller and Luise Borufka and Farahnaz Asghari and Steffen M{\"o}ller and Stephanie-Anna Holzh{\"u}ter and Horst Nizze and Ibrahim, {Saleh M} and Robert Jaster",
year = "2015",
doi = "10.1371/journal.pone.0136298",
language = "English",
volume = "10",
pages = "e0136298",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis

AU - Bischof, Julia

AU - Müller, Sarah

AU - Borufka, Luise

AU - Asghari, Farahnaz

AU - Möller, Steffen

AU - Holzhüter, Stephanie-Anna

AU - Nizze, Horst

AU - Ibrahim, Saleh M

AU - Jaster, Robert

PY - 2015

Y1 - 2015

N2 - 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+ Tregs were observed. In conclusion, CD4+/CD44high memory T cells are the only leukocyte subtype that could be linked to AIP both by correlation studies and from observed overlapping QTL. The potential role of this cell type in the pathogenesis of AIP warrants further investigations.

AB - 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+ Tregs were observed. In conclusion, CD4+/CD44high memory T cells are the only leukocyte subtype that could be linked to AIP both by correlation studies and from observed overlapping QTL. The potential role of this cell type in the pathogenesis of AIP warrants further investigations.

KW - Animals

KW - Antigens, CD44

KW - Autoimmune Diseases

KW - CD4-Positive T-Lymphocytes

KW - Female

KW - Flow Cytometry

KW - Male

KW - Mice

KW - Mice, Inbred Strains

KW - Pancreas

KW - Pancreatitis, Chronic

KW - Quantitative Trait Loci

KW - T-Lymphocyte Subsets

U2 - 10.1371/journal.pone.0136298

DO - 10.1371/journal.pone.0136298

M3 - SCORING: Journal article

C2 - 26325540

VL - 10

SP - e0136298

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 9

ER -