000K  utf8
1100  $c2025
1500  eng
2050  urn:nbn:de:gbv:8:3-2025-00352-7
2051  10.3389/fimmu.2025.1536302
3000  Lukyanov, Daniil K
3010  Blagodatskikh, Konstantin A
3010  Britanova, Olga V
3010  Chudakov, Dmitry M
3010  Fedosova, Anna S
3010  Franke, Andre
3010  Komkov, Alexander Y
3010  Kriukova, Valeriia V
3010  Ladell, Kristin
3010  Minasian, Bella E
3010  Miners, Kelly L
3010  Price, David A
3010  Shagina, Irina A
3010  Shelyakin, Pavel
3010  Staroverov, Dmitry B
3010  Suchalko, Oleg N
4000  Repertoire-based mapping and time-tracking of T helper cell subsets in scRNA-Seq$hFrontiers Media SA  [Lukyanov, Daniil K]
4030  $nFrontiers Media SA
4209  This approach accurately positions the Th1, Th1-17, Th17, Th22, Th2a, Th2, T follicular helper (Tfh), and regulatory T-cell (Treg) subsets, outperforming mapping based on CITE-Seq. Remarkably, the mapping is tightly focused on specific scRNA-Seq clusters, despite 4-year interval between subset sorting and the effector CD4+ scRNA-Seq experiment. These findings highlight the intrinsic program stability of Th clones circulating in peripheral blood. Repertoire overlap analysis at the scRNA-Seq level confirms that the circulating Th1, Th2, Th2a, Th17, Th22, and Treg subsets are clonally independent. However, a significant clonal overlap between the Th1 and cytotoxic CD4+ T-cell clusters suggests that cytotoxic CD4+ T cells differentiate from Th1 clones. In addition, this study resolves a longstanding ambiguity: we demonstrate that, while CCR10+ Th cells align with a specific Th22 scRNA-Seq cluster, CCR10-CCR6+CXCR3-CCR4+ cells, typically classified as Th17, represent a mixture of bona fide Th17 cells and clonally unrelated CCR10low Th22 cells. The clear distinction between the Th17 and Th22 subsets should influence the development of vaccine- and T-cell-based therapies. Furthermore, we show that severe acute SARS-CoV-2 infection induces systemic type 1 interferon (IFN) activation of naive Th cells. An increased proportion of effector IFN-induced Th cells is associated with a moderate course of the disease but remains low in critical COVID-19 cases. Using integrated scRNA-Seq, TCR-Track, and CITE-Seq data from 122 donors, we provide a comprehensive Th scRNA-Seq reference that should facilitate further investigation of Th subsets in fundamental and clinical studies.
4950  https://doi.org/10.3389/fimmu.2025.1536302$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2025-00352-7$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00005883
5051  610
5550  Cytotoxic Cd4+ T Cells
5550  helper T cell subsets
5550  Humans
5550  Immune Repertoires
5550  RNA-Seq
5550  Scrna-seq
5550  Sctcr-seq
5550  Sequence Analysis, RNA
5550  Single-Cell Analysis
5550  Single-Cell Gene Expression Analysis
5550  T cell memory
5550  Th17
5550  Th22
5550  T-Lymphocytes, Helper-Inducer
5550  T-Lymphocyte Subsets