ORCID Profile
0000-0002-5211-518X
Current Organisation
The University of Queensland Diamantina Institute
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Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1016/J.CELREP.2021.109442
Abstract: Transcriptomic analysis plays a key role in biomedical research. Linear dimensionality reduction methods, especially principal-component analysis (PCA), are widely used in detecting s le-to-s le heterogeneity, while recently developed non-linear methods, such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), can efficiently cluster heterogeneous s les in single-cell RNA sequencing analysis. Yet, the application of t-SNE and UMAP in bulk transcriptomic analysis and comparison with conventional methods have not been achieved. We compare four major dimensionality reduction methods (PCA, multidimensional scaling [MDS], t-SNE, and UMAP) in analyzing 71 large bulk transcriptomic datasets. UMAP is superior to PCA and MDS but shows some advantages over t-SNE in differentiating batch effects, identifying pre-defined biological groups, and revealing in-depth clusters in two-dimensional space. Importantly, UMAP generates s le clusters uncovering biological features and clinical meaning. We recommend deploying UMAP in visualizing and analyzing sizable bulk transcriptomic datasets to reinforce s le heterogeneity analysis.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2022
DOI: 10.1038/S41392-022-01147-Z
Abstract: Interleukin 27 (IL-27), a heterodimeric cytokine composed of Epstein-Barr virus-induced 3 and p28, is a pleiotropic cytokine with both pro-and anti-inflammatory properties. However, the precise role of IL-27 in acute graft- versus -host disease is not yet fully understood. In this study, utilizing mice with IL-27 p28 deficiency in dendritic cells (DCs), we demonstrated that IL-27 p28 deficiency resulted in impaired Treg cell function and enhanced effector T cell responses, corresponding to aggravated aGVHD in mice. In addition, using single-cell RNA sequencing, we found that loss of IL-27 p28 impaired Treg cell generation and promoted IL-1R2 + TIGIT + pathogenic CD4 + T cells in the thymus at a steady state. Mechanistically, IL-27 p28 deficiency promoted STAT1 phosphorylation and Th1 cell responses, leading to the inhibition of Treg cell differentiation and function. Finally, patients with high levels of IL-27 p28 in serum showed a substantially decreased occurrence of grade II-IV aGVHD and more favorable overall survival than those with low levels of IL-27 p28. Thus, our results suggest a protective role of DC-derived IL-27 p28 in the pathogenesis of aGVHD through modulation of the Treg/Teff cell balance during thymic development. IL-27 p28 may be a valuable marker for predicting aGVHD development after transplantation in humans.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-02-2023
DOI: 10.1126/SCIIMMUNOL.ADD1728
Abstract: In antibody responses, mutated germinal center B (B GC ) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive selection of B GC cells is controlled by signals received through the B cell receptor (BCR) and follicular helper T (T FH ) cell–derived signals, in particular costimulation through CD40. Here, we demonstrate that the T FH cell effector cytokine interleukin-21 (IL-21) joins BCR and CD40 in supporting B GC selection and reveal that strong IL-21 signaling prioritizes ASC differentiation in vivo. B GC cells, compared with non-B GC cells, show significantly reduced IL-21 binding and attenuated signaling, which is mediated by low cellular heparan sulfate (HS) sulfation. Mechanistically, N-deacetylase and N-sulfotransferase 1 (Ndst1)–mediated N-sulfation of HS in B cells promotes IL-21 binding and signal strength. Ndst1 is down-regulated in B GC cells and up-regulated in ASC precursors, suggesting selective desensitization to IL-21 in B GC cells. Thus, specialized biochemical regulation of IL-21 bioavailability and signal strength sets a balance between the stringency and efficiency of GC selection.
Publisher: Wiley
Date: 2023
DOI: 10.1002/CTI2.1461
Publisher: Cold Spring Harbor Laboratory
Date: 30-11-2022
DOI: 10.1101/2022.11.28.22282728
Abstract: Uveitis is a common cause of blindness and classified as infectious or non-infectious types. Non-infectious uveitis is often secondary to systemic autoimmune diseases, with Behçet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKHD) as the two most common causes. Uveitis in BD and VKHD often show similar clinical manifestations, but the underlying immunopathogenesis remains unclear. We collected immune cell infiltrates in aqueous humour of BD and VKHD uveitis patients and analysed them by single-cell RNA paired with T cell receptor (TCR) sequencing. T cells were found as the dominant immune cell infiltration. Intriguingly, a majority of CD4 + in T cell infiltrates was only observed in VKHD but not in BD. In agreement with this discrepancy between VKHD and BD, T cell clonality analysis and Clonotype Neighbour Graph Analysis (CoNGA) also revealed a selective expansion of pro-inflammatory CD4 + T cell clones in VKHD. In contrast, BD showed a selective expansion of pro-inflammatory CD8 + T cell clones. Our study reveals distinct immunopathogenesis of uveitis driven by CD4 + T cells in VKHD and by CD8 + T cells in BD, and therefore suggests differential approaches for their diagnosis and therapy.
Location: Australia
No related grants have been discovered for Hongjian Sun.