Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays

AbstractThe liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oligonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon γ (IFN-γ)–inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-γ protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN-γ early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD.

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Equine mesenchymal stromal cells from different tissue sources display comparable immune-related gene expression profiles in response to interferon gamma (IFN)-γ

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2018.06.008 ◽

2018 ◽

Vol 202 ◽

pp. 25-30 ◽

Cited By ~ 7

Author(s):

Jennifer M. Cassano ◽

Lisa A. Fortier ◽

Rebecca B. Hicks ◽

Rebecca M. Harman ◽

Gerlinde R. Van de Walle

Keyword(s):

Gene Expression ◽

Interferon Gamma ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Related Gene ◽

Immune Related Gene ◽

Ifn Γ

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The Predictive Value of Gene Expression Profiles for Acute Graft-Versus-Host Disease after Hematopoietic Cell Transplantation with Nonmyeloablative Conditioning for Hematological Malignancy.

Blood ◽

10.1182/blood.v110.11.1079.1079 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1079-1079

Author(s):

Tania N. Masmas ◽

Lennart Friis-Hansen ◽

Jens Vilstrup Johansen ◽

Soren Lykke Petersen ◽

Brian T. Kornblit ◽

...

Keyword(s):

Gene Expression ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Hematopoietic Cell Transplantation ◽

Late Onset ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Graft Versus Host ◽

Post Transplant ◽

Acute Graft

Abstract Purpose: To test the hypothesis that global gene expression profiles of peripheral blood mononuclear cells (PBMNC) day +14 after hematopoietic cell transplantation with nonmyeloablative conditioning could predict the later occurrence of acute graft-versus-host disease (GVHD) grade II–IV. Material: Between March 2000 and Marts 2006, 100 patients with hematological malignancies received peripheral blood stem cells from an human leukocyte antigen identical sibling/mother donor or from a matched unrelated donor following nonmyeloablative conditioning with low dose fludarabine and 2 Gy of total body irradiation. Post-transplant immunosuppression consisted of cyclosporine and mycophenolate mofetil. Only patients with sustained engraftment, who did not experience late-onset acute GVHD after day +100 were included; eight patients were excluded due to graft rejection, three patients due to suboptimal RNA or lacking PBMNC samples, and further 15 patients due to late-onset acute GVHD. Seventy-four patients were then eligible for microarray analysis. Methods: RNA was precipitated from frozen PBMNC from day +14 post-transplant and gene profiling analyses were performed using Human Genome U133 Plus 2.0 GeneChip Array. The array data were normalized, RMA modelled and asinh transformed in R. The differentially regulated gene expression between the group of patients developing acute GVHD before day +40, +56 and +84 post-transplant compared to the patients never experiencing acute GVHD was identified and formed the basis for the subsequent principal component analysis (PCA) and classifying models. No patients experienced acute GVHD between day +85 and +100 post-transplant. Results: The patients experiencing acute GVHD by different time points were separated from the patients never experiencing acute GVHD by the PCA plot. Furthermore the classifying models could separate the groups correctly in up to 93% of cases in the best of the classifying model. In addition, differentially regulated genes between the two groups were identified. Conclusion: These data suggest that the pattern of gene expression profiles early post-transplant is able to predict patients with a high risk of later occurrence of acute GVHD from those never experiencing acute GVHD. This knowledge could be exploited to increase the immunosupression and thus prevent acute GVHD in patients at risk. Furthermore, candidate genes of interest for the pathogenesis of acute GVHD have been identified.

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Altered endometrial immune gene expression in beef heifers with retarded embryos

Reproduction Fertility and Development ◽

10.1071/rd12232 ◽

2013 ◽

Vol 25 (6) ◽

pp. 966 ◽

Cited By ~ 11

Author(s):

M. E. Beltman ◽

N. Forde ◽

P. Lonergan ◽

M. A. Crowe

Keyword(s):

Gene Expression ◽

Transforming Growth Factor ◽

Expression Profiles ◽

Survival Rates ◽

Gene Expression Profiles ◽

Immune Gene ◽

Beef Heifers ◽

Cell Stage ◽

Embryo Survival ◽

Ifn Γ

The aim of the present study was to compare endometrial gene expression profiles in a group of beef heifers yielding viable or retarded embryos on Day 7 after oestrus as a means of potentially explaining differences in embryo survival rates. Heifers were classified as either: (1) viable, when the embryo collected on Day 7 after oestrus was at the correct developmental stage (i.e. morula/early blastocyst); or (2) retarded, when the embryo was arrested at the 2–16-cell stage. The focus of the present study was on genes that were associated with either the pro- or anti-inflammatory immune response. Endometrial gene expression was determined using quantitative real-time polymerase chain reaction analysis. Expression of the β-defensin (DEFB1), interferon (IFN)-α (IFNA), IFN-γ (IFNG), interleukin (IL)-6 (IL6), IL-10 (IL10), forkhead box P3 (FOXP3) and natural cytotoxicity triggering receptor 1 (NCR1) genes was lower in endometria from viable than retarded heifers. Expression of the nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (NKFB1), transforming growth factor (TGF)-β (TGFB), IFN-γ-inducible protein 16 (IFI16) and IL-21 (IL21) genes was higher in viable than retarded heifers. We propose that small disturbances in the expression of immune genes in the endometrium on Day 7 after oestrus can have detrimental effects on embryo survival.

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In Vivo Permanent Marking of Cells with RAG1 Activation History Demonstrates That Lymphoid and Myeloid Derived Dendritic Cells Operate an Identical Developmental Program after Their Lineage Commitment.

Blood ◽

10.1182/blood.v110.11.1328.1328 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1328-1328

Author(s):

Yong Chong ◽

Tadafumi Iino ◽

Shin-ichi Mizuno ◽

Hirokazu Shigematsu ◽

Yojiro Arinobu ◽

...

Keyword(s):

Gene Expression ◽

Dendritic Cells ◽

Mhc Class Ii ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Yellow Fluorescence Protein ◽

Developmental Program ◽

A Genome ◽

Unique Cell

Abstract Dendritic cells (DCs) have been shown to arise from both myeloid and lymphoid pathways, by evaluating the in vivo reconstituting potential of myeloid- and lymphoid-committed progenitor populations. However, evaluation of DC development after conventional adoptive transfer experiments may not correctly represent normal DC development including lineage contribution toward the formation of the DC pool. By crossing RAG1-Cre knockin with yellow fluorescence protein (YFP)-floxed reporter lines, we developed a mouse line in which cells with a history of RAG activation should be permanently marked with YFP as a result of lymphoid commitment. Lymphoid-derived DCs were successfully marked as YFP+ in vivo. We found that only ∼10% of conventional DCs (cDCs) and ∼20% of plasmacytoid DCs (pDCs) were YFP+, even in the thymus. This is a formal evidence that the majority of DCs in steady-state hematopoiesis originate from stages that have committed to the myeloid lineage. The lineage origin of DCs did not affect their functional abilities, including antigen-presentation and cytokine production. We then profiled the gene expression of the YFP+ and YFP- DCs at a genome wide level by DNA microarray analysis. Unexpectedly, the gene expression profiles of lymphoid and myeloid-derived DCs were virtually identical, irrespective of their organs. In contrast, the genetic programs were apparently different between splenic and thymic DCs, regardless of their lineage origin. Moreover, thymic DCs contained a number of more activated genes, such as MHC class II-related ones, as compared to splenic DCs. These results suggest that lymphoid and myeloid DCs might use a common developmental program that can be activated even after lymphoid or myeloid commitment. Thus, DCs are a unique cell population independent of other conventional lineage cells. Lineage-restricted DCs might be merged into an identical pool, distributed to various tissues, and finally fated by the microenvironment of their sites.

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