Project description:Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAITCAST mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-β. Interactome analysis predicts CXCR6 – CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6+ MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.
Project description:This experiment captures the expression data obtained from mouse cerebellar granule neurons (CGN) at different time points of post-natal development, both in wild type samples (P0, P7, and P15) and in CGN electroporated with vectors expressing transcription factors Zeb1 and Hes1 (both P7).
Project description:This project applies SWATH approach to analyse ex-diagnostic sheep serum samples from actual clinical cases submitted to The University of Queensland's School of Veterinary Science, Veterinary Laboratory Services (VLS) compared with serum of normal sheep.
Project description:This project deals with the characterisation and establishment of the baseline circulating acellular proteome of sheep serum using generic methods. Serum is a readily available substrate for most experimental and clinical applications as evidenced in recent sheep studies. It involves sample preparation for the optimisation of proteomic profiling of sheep serum. The chapter therefore represents the first step in the development of a proteomics pipeline for the detection protein alterations by first establishing the normal proteomic profile of sheep serum.
Project description:This program aims at identifying a skin gene signature associated with inflammation pain in rat CGN model The profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in the skin of rats treated with CGN (to induce pain) compared to the corresponding non-treated controls.
Project description:Within a project aim to define the genomic aberration of thymic epithelial tumors, we performed array CGH in 65 thymic epithelial tumors. Tumor samples were collected during surgery or by image-guided biopsies and immediately frozen. Section from frozen material were cut and stained with Haematoxylin and Eosin. A pathologist reviewed the slides and selected only cases with >80% of cancer cells.
Project description:To further reveal the key genes and related microRNAs involved in the CGN and to determine the potential molecular mechanisms of CGN pathogenesis. We have employed microarray expression profiling as a discovery platform to identify genes and related microRNAs. To identify the key ceRNA in CGN, we generated a ceRNA network using data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO). 2334 differentially regulated genes and a total of 673 related miRNAs were identified. We found that the ceRNA network was composed of 31 lncRNAs, 344 mRNAs, and 57 miRNAs. Expression of five genes (FOS, SYK, CYP1A1, HSD3B6, UGT2B15), five microRNAs (miR-34a-5p, miR-214-3p, miR-155-5p, miR-182, miR-592), three lncRNAs (LOC102547703, NONRATT006779, FQ220365) were quantified in the same RNA samples by real-time PCR, which could be potential diagnostic biomarkers and therapeutic targets for CGN.