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
Leif Wigge
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
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) 17487838 (eISSN)
Vol. 31 5 554-568Subject 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