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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression in the thymus medulla in the absence and presence of acute graft-versus-host disease

ABSTRACT: To investigate gene expression profile of medullary thymic epithelial cells with high surface density of MHC class II (mTEChigh), a murine parent into F1 hematopoietic stem cell transplantation model was administered. As recipient mice (B6xDBA/2)F1 (B6D2F1) were used that received either a syngeneic transplant from a (B6xDBA/2)F1 mouse or an allogeneic transplant from a B6 mouse, which leads to acute graft-versus-host disease (aGVHD). mTEChigh (CD45-EpCAM+Ly51-UEA1+MHCIIhigh) are sorted by FACS.

ORGANISM(S): Mus musculus

SUBMITTER: Simone Dertschnig

PROVIDER: E-MEXP-3745 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Epithelial cytoprotection sustains ectopic expression of tissue-restricted antigens in the thymus during murine acute GVHD.

Dertschnig Simone S Nusspaumer Gretel G Ivanek Robert R Hauri-Hohl Mathias M MM Holländer Georg A GA Krenger Werner W

Blood 20130529 5

Development of acute graft-versus-host disease (aGVHD) predisposes to chronic GVHD with autoimmune manifestations. A characteristic of experimental aGVHD is the de novo generation of autoreactive T cells. Central tolerance is dependent on the intrathymic expression of tissue-restricted peripheral self-antigens (TRA), which is in mature medullary thymic epithelial cells (mTEC(high)) partly controlled by the autoimmune regulator (Aire). Because TECs are targets of donor T-cell alloimmunity, we tes ...[more]

PMID: 23719300

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Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys Immunobiology

Project description:Acute rejection episodes trigger chronic renal allograft vasculopathy. Numerous leukocytes, predominantly monocytes, accumulate in graft blood vessels during reversible acute rejection preceding chronic rejection of rat kidneys. We speculate that they contribute to transplant vasculopathy and set out to characterize them. Allogeneic renal transplantation was performed in the Fischer 344 to Lewis rat strain combination, Lewis isografts served as controls. Leukocytes were harvested by intensive perfusion of graft blood vessels and subjected to flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling. Kidneys of LEW and F344 rats were transplanted in LEW rats. Five biological replicates were performed for both isogenic and allogenic transplantation. Transcriptomes of allogenics were compared to isogenics on 5 dual-color hybridizations.

2010-09-24 | E-GEOD-18266 | biostudies-arrayexpress

Redefining thymus medulla specialization for central tolerance.

Project description:During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3+ T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.

| S-EPMC5679166 | biostudies-literature

promiscuous gene expression in the mouse thymus

Project description:Gene expression in different thymic stromal cells and subsets thereof was analyzed in 6-12 week old wild type (C57BL/6) and Aire knock-out (mixed background) mice. Thymic stromal cells were purified by sequential enzymatic digestion (collagenase, collagenase/dispase and trypsin) followed by gradient centrifugation and FACS sorting. Sort criteria were as follows: dendritic cells (CD11c+, F4/80 -), macrophages (F4/80+, CD11c-), cTECs (CD45–/lo, CDR1/Ly51+, Ep-CAM+) and mTECs (CD45–/lo, CDR1/Ly51–, Ep-CAM+). mTECs of wild-type and Aire knock-out mice were further subdivided according to CD80 expression levels. For microarray analysis total RNA from thymic stromal cell samples of two independent experiments was pre-amplified and biotinylated by two rounds of cDNA synthesis and in vitro transcription. Fluorescence readings were evaluated by using Microarray Suite 5.0 software. Keywords = thymus Keywords = promiscuous gene expression Keywords = AIRE Keywords: ordered

2005-04-28 | GSE2585 | GEO

The effect of cortex/medulla proportions on molecular diagnoses in kidney transplant biopsies: rejection and injury can be assessed in medulla

Project description:Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL and REN. Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the Molecular Microscope Diagnostic System. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had <50% cortex. Molecular scores for ABMR, TCMR, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection, and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex. We studied 26 pairs of cortex/medulla biopsies from 26 patients (4 unpaired), characterizing the clinical and histological features, and defined the mRNA phenotype with Affymetrix expression microarrays. We also studied 37 pairs of biopsies from biological replicates and 12 pairs from technical replicates. This dataset is part of the TransQST collection.

2017-04-27 | E-GEOD-95611 | biostudies-arrayexpress

Subclinical effects of remote ischaemic conditioning in human kidney transplants revealed by quantitative proteomics

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2021-09-09 | PXD019284 | Pride

Leptin receptor is expressed in thymus medulla and leptin protects against thymic remodeling during endotoxemia-induced thymus involution.

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The medulla controls effector primed γδT-cell development in the adult mouse thymus.

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2023-02-15 | E-MTAB-12282 | biostudies-arrayexpress

Dynamic spatio-temporal contribution of single β5t+ cortical epithelial precursors to the thymus medulla.

Project description:Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit β5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that β5t(+) TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely formed. Lineage-tracing studies at single cell resolution demonstrate for young mice that the postnatal medulla is expanded from individual β5t(+) cortical progenitors located at the cortico-medullary junction. These results therefore not only define a developmental window during which the expansion of medulla is efficiently enabled by progenitors resident in the thymic cortex, but also reveal the spatio-temporal dynamics that control the growth of the thymic medulla.

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Transcription profiling of mouse acute lymphoblastic leukemia in vivo after allogeneic or syngeneic bone marrow transplantation

Project description:This study compared gene expression in murine bcr-abl positive acute lymphoblastic leukemia cells in vivo in allogeneic BMT recipients compared to syngneneic BMT recipients. Experiment Overall Design: The goal of the experiment was to compare gene expression in leukemia cells that were in either an allogeneic transplant (5 samples) or syngeneic transplant (5 samples) immune environment in vivo. The bone marrow transplant model involved preparation of C57BL/6 recipients with total body irradiation and 5-fluoruracil. These recipients were then infused IV with either allogeneic C3.SW marrow and spleen cells or syngeneic C57BL/6 marrow and spleen cells. The leukemia cells were mixed in with the marrow and spleen cells. After a few weeks (2-3) the C57BL/6 leukemia cells were purified by flow cytometry and passed into other freshly transplanted animals. After three serial transplants the leukemia cells were flow purified and RNA prepared. Leukemia was C57BL/6 background (cells contain the human p210 bcr/abl oncogenic fusion gene and also have a deletion in the Ink4a/Arf locus, see: Biology of Blood and Marrow Transplantation. 14:622-630, 2008).

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