Pathogenetic role of an autoimmune susceptibility locus derived from MRL/MpJ strain chromosome 1 in chronic pancreas inflammation

Okada, Yuki; Nakamura, Teppei; Ichii, Osamu; Otsuka, Saori; Kon, Yasuhiro

doi:10.1177/0961203314536249

Cited by 2 publications

(1 citation statement)

References 35 publications

(51 reference statements)

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“…Recently, Okada et al . reported a pathogenetic role of mag , an autoimmune susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in murine AIP [ 34 ]. Interestingly, this susceptibility locus is not preserved in our intercross line since we did not map significant genetic markers on chromosome 1.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis

Sandy

Chan

Trevino

et al. 2015

Osteoarthritis and Cartilage

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A major objective of this article is to examine the research implications of recently available genome-wide expression profiles of cartilage from human osteoarthritis (OA) joints. We propose that when viewed in the light of extensive earlier work this novel data provides a unique opportunity to reorient the design of experimental systems toward clinical relevance. Specifically, in the area of cartilage explant biology this will require a fresh evaluation of existing paradigms, so as to optimize the choices of tissue source, cytokine/growth factor/nutrient addition, and biomechanical environment for discovery. Within this context, we firstly discuss the literature on the nature and role of potential catabolic mediators in OA pathology, including data from human OA cartilage, animal models of OA and ex vivo studies. Secondly, due to the number and breadth of studies on IL-1β in this area, a major focus of the article is a critical analysis of the design and interpretation of cartilage studies where IL-1β has been used as a model cytokine. Thirdly, the article provides a data-driven perspective (including genome-wide analysis of clinical samples, studies on mutant mice, and clinical trials), which concludes that IL-1β should be replaced by soluble mediators such as IL-17 or TGF-β1, which are much more likely to mimic the disease in OA model systems. We also discuss the evidence that changes in early OA can be attributed to the activity of such soluble mediators, whereas late-stage disease results more from a chronic biomechanical effect on the matrix and cells of the remaining cartilage and on other local mediator-secreting cells. Lastly, an updated protocol for in vitro studies with cartilage explants and chondrocytes (including the use of specific gene expression arrays) is provided to motivate more disease-relevant studies on the interplay of cytokines/growth factors and biomechanics on cellular behavior.

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Pathogenetic role of an autoimmune susceptibility locus derived from MRL/MpJ strain chromosome 1 in chronic pancreas inflammation

Abstract: 18We examined the role of Mag, an autoimmune susceptibility locus encoded by the telomeric 19 region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune 20 exocrinopathy. At 9-12 months of age, strain-specific differences were observed in the

Cited by 2 publications

References 35 publications

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

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

Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis

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