Th2 single-cell heterogeneity and clonal distribution at distant sites in helminth-infected mice

Abstract
Data availability
Article and author information

Abstract

Th2 cells provide effector functions in type 2 immune responses to helminths and allergens. Despite knowledge about molecular mechanisms of Th2 cell differentiation, there is little information on Th2 cell heterogeneity and clonal distribution between organs. To address this, we performed combined single-cell transcriptome and TCR clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLN) and lung after infection with Nippostrongylus brasiliensis (Nb) as a human hookworm infection model. We find organ-specific expression profiles, but also populations with conserved migration or effector/resident memory signatures that unexpectedly cluster with potentially regulatory Il10^posFoxp3^neg cells. A substantial MLN subpopulation with an interferon response signature suggests a role for interferon-signaling in Th2 differentiation or diversification. Further RNA-inferred developmental directions indicate proliferation as a hub for differentiation decisions. Although the TCR repertoire is highly heterogeneous, we identified expanded clones and CDR3 motifs. Clonal relatedness between distant organs confirmed effective exchange of Th2 effector cells, although locally expanded clones dominated the response. We further cloned an Nb-specific TCR from an expanded clone in the lung effector cluster and describe surface markers that distinguish transcriptionally defined clusters. These results provide insights in Th2 cell subset diversity and clonal relatedness in distant organs.

Data availability

Single-cell RNA sequencing data is available via GEO with the ID GSE181342

The following data sets were generated

(2021) Th2 single-cell heterogeneity and clonal interorgan distribution in helminth-infected mice
NCBI Gene Expression Omnibus, GSE181342.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE181342

Article and author information

Author details

Daniel Radtke

Department of Infection Biology, University of Erlangen-Nuremberg, Erlangen, Germany

For correspondence
daniel.radtke@uk-erlangen.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3241-4542
Natalie Thuma

Department of Infection Biology, University of Erlangen-Nuremberg, Erlangen, Germany

Competing interests
The authors declare that no competing interests exist.
Christine Schülein

Institute of Clinical Microbiology, University of Erlangen-Nuremberg, Erlangen, Germany

Competing interests
The authors declare that no competing interests exist.
Philipp Kirchner

Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany

Competing interests
The authors declare that no competing interests exist.
Arif B Ekici

Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany

Competing interests
The authors declare that no competing interests exist.
Kilian Schober

Institute of Clinical Microbiology, University of Erlangen-Nuremberg, Erlangen, Germany

Competing interests
The authors declare that no competing interests exist.
David Voehringer

Department of Infection Biology, University of Erlangen-Nuremberg, Erlangen, Germany

For correspondence
David.Voehringer@uk-erlangen.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6650-0639

Funding

Deutsche Forschungsgemeinschaft (RTG1660)

David Voehringer

Deutsche Forschungsgemeinschaft (FOR2599_TP4)

David Voehringer

Deutsche Forschungsgemeinschaft (TRR130_TP20)

David Voehringer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed in accordance with German animal protection law and European Union guidelines 86/809 and were approved by the Federal Government of Lower Franconia.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.