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

Radtke D, Thuma N, Schülein C, Kirchner P, Ekici AB, Schober K, Vöhringer D (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 11

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 T-cell receptor (TCR) clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLNs) 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(pos)Foxp3(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.

Authors with CRIS profile

Daniel Radtke Department of Infection Biology Natalie Thuma Department of Infection Biology Christine Schülein Lehrstuhl für Bioverfahrenstechnik Arif Bülent Ekici Lehrstuhl für Humangenetik Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene David Vöhringer Professur für Infektionsabwehr und Toleranz

How to cite

APA:

Radtke, D., Thuma, N., Schülein, C., Kirchner, P., Ekici, A.B., Schober, K., & Vöhringer, D. (2022). Th2 single-cell heterogeneity and clonal distribution at distant sites in helminth-infected mice. eLife, 11. https://dx.doi.org/10.7554/eLife.74183

MLA:

Radtke, Daniel, et al. "Th2 single-cell heterogeneity and clonal distribution at distant sites in helminth-infected mice." eLife 11 (2022).

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