TCR repertoire analysis reveals effector memory T cells differentiation into Th17 cells in rheumatoid arthritis

Abstract

contributed equally to this work. Abstract: The pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4+ T-cell subsets could help understand RA pathogenesis.Here, peripheral CD4+ T cells from treatment-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor β chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells, with highly similar TCR repertoires between them.Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Moreover, TCR diversity in subsets including Th17 was negatively

Understanding neural development and diseases using CRISPR screens in human pluripotent stem cell-derived cultures

“…Recent versions of genome-wide CRISPR libraries have generated optimized sgRNA libraries with improved efficiencies and reduced off-target activities (Doench et al, 2016;Hart et al, 2017;Henkel et al, 2020). Combined with the improved algorithms for data analysis (Wang et al, 2019;Kim and Hart, 2021), it is now feasible to perform essentiality screens with higher dynamic range and reduced library coverage. It is worth mentioning that by adjusting the dynamic range of a CRISPR screen, it is possible to perform both positive and negative selections in a single screen.…”

Factors regulating the differences in frequency of infiltration of Th17 and Treg of the blood–brain barrier

“…The differences in the sequences of CDR3 (TCR complex) and the genes DP, DQ, and DR (MHCII) between Th17 and Tregs could be one of the leading factors supporting Th17 infiltrative capacity of the brain. In rheumatoid arthritis, where an unbalance between Th17 and Treg has been shown to influence the disease outcome, it has been revealed that the diversity of the Th17 was less in RA than in healthy controls (26). Conversely, the case was reversed among Tregs repertoire, indicating higher clonality among Th17 but not within Tregs.…”

Thermophilic Fungus Uses Anthraquinones to Modulate Ferrous Excretion, Sterol-Mediated Endocytosis and Iron Storage in Response to Cold Stress

“…8 Our recent studies have shown that both Thermomyces species displayed much darker colonies at minimum growth temperature of 37 °C compared to their optimal growth temperature of 45 °C. 10,11 Among them, T. lanuginosus accumulated a melanin precursor, a polyketide derived dihydroxynaphthalene metabolite TDN. 10 Through construction of the mutant ∆Tdn with the disruption of the polyketide synthase (PKS) gene Tdn, metabolic and transcriptional analysis, and a series of phenotypic and physiological bioassays, we found that TDN was involved in reinforcing fungal cell wall, inhibiting lipid formation and iron levels, and scavenging reactive oxygen species (ROS) to defend cold stress-induced ferroptosis.…”

“…10,11 Among them, T. lanuginosus accumulated a melanin precursor, a polyketide derived dihydroxynaphthalene metabolite TDN. 10 Through construction of the mutant ∆Tdn with the disruption of the polyketide synthase (PKS) gene Tdn, metabolic and transcriptional analysis, and a series of phenotypic and physiological bioassays, we found that TDN was involved in reinforcing fungal cell wall, inhibiting lipid formation and iron levels, and scavenging reactive oxygen species (ROS) to defend cold stress-induced ferroptosis. 10 This study suggested that Thermomyces species should be an ideal model for deciphering physiological and biological functions of secondary metabolites in fungal adapt to temperature changes.…”

“…10 Through construction of the mutant ∆Tdn with the disruption of the polyketide synthase (PKS) gene Tdn, metabolic and transcriptional analysis, and a series of phenotypic and physiological bioassays, we found that TDN was involved in reinforcing fungal cell wall, inhibiting lipid formation and iron levels, and scavenging reactive oxygen species (ROS) to defend cold stress-induced ferroptosis. 10 This study suggested that Thermomyces species should be an ideal model for deciphering physiological and biological functions of secondary metabolites in fungal adapt to temperature changes. Interestingly, T. dupontii at the minimum growth temperature of 37 °C accumulated two types of metabolites, including nonribosomal peptides-terpenoid (NRP-TP) hybrid prenyl indole alkaloids (PIAs) and polyketide derived anthraquinones.…”