Wang, L. Z. | Search bioRxiv

bioRxiv2026

Mucosal-Associated Invariant T Cells Promote Atherosclerosis Through Monocyte-Driven Inflammation

Mucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes that may contribute to inflammatory responses, although their specific role in atherosclerosis remains poorly understood. In this study, we identified MAIT cells within human atherosclerotic plaques and found that they were significantly enriched among CD3 T cells in plaques compared to matched peripheral blood samples. MAIT cells within plaques exhibited an activated phenotype and showed upregulation of genes associated with inflammation and cellular activation, compared to circulating MAIT cells from the same patients. Using murine models, we found that low-density lipoprotein receptor (Ldlr)-/- mice carrying the CAST locus, which confers naturally higher frequencies of MAIT cells, displayed increased MAIT cell accumulation in both the liver and atherosclerotic plaques when fed a high-cholesterol diet. In contrast, MAIT cell-deficient Ldlr-/-CAST MR1-/- mice exhibited a reduced atherosclerotic burden, diminished liver fibrosis, smaller myocardial infarcts following coronary artery ligation, without significant changes in plasma cholesterol levels. These atheroprotective effects were accompanied by lower monocyte counts in the bone marrow and blood, as well as reduced plaque macrophage accumulation in the plaques. Furthermore, deletion of CCR2, which impairs monocyte mobilization, abrogated the pro-atherogenic effects of MAIT cells, indicating that MAIT-driven atherogenesis occurs through a monocyte-dependent mechanism. Taken together, these findings identify MAIT cells as active contributors to vascular inflammation and position them as potential therapeutic targets for atherosclerosis and its complications.

immunology↗

bioRxiv2018

Artificial Selection on Storage Protein 1 Contributes to Increase of Hatchability during Silkworm Domestication

Like other domesticates, efficient utilization of nitrogen resource is also important for the domestic insect, the silkworm. Deciphering how artificial selection act on silkworm genome for improved utilization of nitrogen resource and further human-favored domestication traits will provide unique cues from the insect scenario for understanding general rules of Darwins evolutionary theory on domestication. Storage proteins (SP), which belong to a hemocyanin superfamily, basically serve as a source of amino acids and nitrogen during metamorphosis and reproduction in insects. Here through genomic search and further screening of artificial selection signature on silkworm SPs, we discovered a candidate domestication gene, i.e. the methionine-rich storage protein1 (SP1), which is uniquely diverged from the others and showed increased expression in the ova of domestic silkworms. Knockout of SP1 via CRISPR/Cas9 approach resulted in dramatic decrease in egg hatchability, without obvious impact on egg production, which was similar to the case in the wild silkworm compared with domestic one. Larval development or metamorphosis were not affected by SP1 knockout. Comprehensive ova comparative transcriptomes indicated a general repression of gene expression, specifically vitellogenin, chorion proteins and structural component proteins in the extracellular matrix (ECM)-interaction pathway, as well as enzymes in folate biosynthesis, in both the mutant and the wild silkworm with the mutated allele, compared to the wild type domestic silkworm. Wild silkworms with the wild allele also showed generally down-regulated expression of genes enriched in structural constituent of ribosome and amide and peptide biosynthesis. This study exemplified a novel case that artificial selection could directly act on nitrogen resource protein to affect egg nutrient and eggshell formation, and activate ribosome for improved biosynthesis and increased hatchability during domestication. The findings shed new light on both understanding of artificial selection and silkworm breeding from the angle of nitrogen and amino acid resource.\n\nAuthor summaryLike other domesticates, nitrogen resource is also important for the domestic insect, the silkworm. Deciphering how artificial selection act on silkworm genome for improved utilization of nitrogen resource and further human-favored domestication traits, will provide unique cues from insect scenario, for understanding general rules of Darwins evolutionary theory. However, mechanism of domestication in the silkworm is largely unknown to date. Here we focused on one important nitrogen resource, i.e, the storage proteins (SP). We discovered that the methionine-rich storage protein1 (SP1) which is divergent from the other SPs are the only target of the artificial selection. We proposed based on functional evidence together with the key findings of comprehensive comparative transcriptome, that artificial selection, on one hand favored higher expression of SP1 in the domestic silkworm, which would subsequently up-regulate the genes or pathways vital for egg development and eggshell formation. On the other hand, artificial selection consistently favored activated ribosome activities and improved amide and peptide biosynthesis and in the ova, as it might act in the silk gland for increased silk-cocoon yield. We here exemplified a novel case that artificial selection could directly act on nitrogen resource protein for human desired domestication trait.

evolutionary biology↗