Repertoire-based mapping and time-tracking of T helper cell subsets in scRNA-Seq

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143863" target="_blank" >RIV/00216224:14740/25:00143863 - isvavai.cz</a>

Result on the web

<a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1536302/full" target="_blank" >https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1536302/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fimmu.2025.1536302" target="_blank" >10.3389/fimmu.2025.1536302</a>

Result language

angličtina

Original language name

Repertoire-based mapping and time-tracking of T helper cell subsets in scRNA-Seq

Original language description

Introduction The functional programs of CD4+ T helper (Th) cell clones play a central role in shaping immune responses to different challenges. While advances in single-cell RNA sequencing (scRNA-Seq) have significantly improved our understanding of the diversity of Th cells, the relationship between scRNA-Seq clusters and the traditionally characterized Th subsets remains ambiguous.Methods In this study, we introduce TCR-Track, a method leveraging immune repertoire data to map phenotypically sorted Th subsets onto scRNA-Seq profiles.Results and discussion 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in immunology

ISSN

1664-3224

e-ISSN

—

Volume of the periodical

16

Issue of the periodical within the volume

Apr

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

1-15

UT code for WoS article

001469160900001

EID of the result in the Scopus database

2-s2.0-105003020036