Author: Rami Bechara
Hou et al. (0733) utilised CRISPR/Cas9 technology to identify cell type-specific functional variants that regulate the Type I interferon pathway in lupus. Notably, they discovered the negative regulatory effect of the SNP rs11152966 on the Type I interferon pathway and identified PRDM1 as the target gene.
Laragione et al. (0793) identified the dual specificity phosphatase 6 (DUSP6) as a key regulator of rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) invasiveness and arthritis severity. In a mouse model of arthritis, DUSP6 knockout mice exhibited milder disease, increased regulatory T cell populations, higher IL10 levels, and reduced IL6.
Philippon et al (0798) aimed to develop a novel 3D-spheroid model mimicking rheumatoid arthritis (RA). The model included monocyte-derived macrophages, RA fibroblast-like synoviocytes (RAFLS), and endothelial cells (ECs). The spheroid-based model demonstrated close interaction between macrophages, RAFLS, and ECs, providing a valuable tool for studying inflammatory responses in RA pathogenesis.
Abdukiyum et al. (0931) investigated the impact of N6-methyladenosine (m6A) modifications on mitochondrial abnormalities in systemic lupus erythematosus (SLE) CD4+ T cells. Methylated RNA immunoprecipitation sequencing revealed differential m6A methylation, including the mitochondrial gene MT-ND6. The low expression of MT-ND6 in lupus patients was associated with mitochondrial dysfunction in CD4+ T cells, leading to increased reactive oxygen species, and enhanced inflammatory responses.
Barker et al. (1738) aimed to characterise synovial fibroblast populations in the synovial tissue of healthy controls (HC) and RA patients. Using single-cell RNA sequencing and flow cytometric analysis, the researchers identified 14 FLS clusters broadly aligned to four main subsets, with six clusters more prevalent in RA and eight in HC synovium.
Parisis et al. (2192) established an inducible model for primary Sjögren’s syndrome (pSS) using mice. Female C57Bl/6 mice were treated with 5,6-dimethylxanthenone-4-acetic acid DMXAA. The induced model exhibited key features of human pSS, including reduced salivary and lacrimal flow, focal sialadenitis, and increased anti-Ro/SSA antibodies.
Zhao et al. (2443) investigated the effects of OX40L blockade using anti-OX40L in the MRL/lpr murine lupus model and found that the treatment delayed disease progression, reducing anti-dsDNA antibodies, proteinuria, and Ig deposition in the kidney. In vitro experiments indicated that anti-OX40L promoted regulatory T cell differentiation and inhibited TLR7-mediated antibody-secreting cell differentiation, suggesting OX40L blockade as a promising strategy to mitigate SLE pathology.
ABOUT THE AUTHOR
Rami Bechara
Rami is an Assistant Professor in Immunology at Paris-Saclay University, Paris, France. His research delves into understanding the implication of post-transcriptional regulation in autoimmune diseases, mainly Sjogren’s Syndrome.
Aside from his activities as researcher, Rami is the first president-elect of the young European Federation of Immunological Societies, yEFIS.