Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
Journal article, 2021

The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.

Author

Luca Mazzurana

Karolinska Institutet

Paulo Czarnewski

Stockholm University

Viktor Jonsson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology, CSBI

Leif Wigge

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology, CSBI

Markus Ringnér

Lund University

Teresa C. Williams

Karolinska Institutet

Avinash Ravindran

Karolinska University Hospital

Åsa K. Björklund

Uppsala University

Jesper Säfholm

Karolinska Institutet

Gunnar Nilsson

Karolinska University Hospital

Sven Erik Dahlén

Karolinska Institutet

Ann Charlotte Orre

Karolinska University Hospital

Mamdoh Al-Ameri

Karolinska University Hospital

Karolinska Institutet

Charlotte Höög

Karolinska Institutet

Charlotte Hedin

Karolinska University Hospital

Karolinska Institutet

Sylwester Szczegielniak

Karolinska University Hospital

Sven Almer

Karolinska Institutet

Karolinska University Hospital

Jenny Mjösberg

Karolinska Institutet

Cell Research

1001-0602 (ISSN)

Vol. 31 5 554-568

Subject Categories

Immunology

Cell and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1038/s41422-020-00445-x

PubMed

33420427

More information

Latest update

8/17/2021