Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues

Friedrich C, Taggenbrock RLRE, Doucet-Ladeveze R, Golda G, Moenius R, Arampatzi P, Kragten NAM, Kreymborg K, De Agueero MG, Kastenmueller W, Saliba AE, Gruen D, Van Gisbergen KPJM, Gasteiger G (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Immunology Nature Research

Book Volume: 22

Pages Range: 1256-1267

Journal Issue: 10

DOI: 10.1038/s41590-021-01013-0

Abstract

Innate lymphoid cells (ILCs) participate in tissue homeostasis, inflammation, and early immunity against infection. It is unclear how ILCs acquire effector function and whether these mechanisms differ between organs. Through multiplexed single-cell mRNA sequencing, we identified cKit⁺CD127^hiTCF-1^hi early differentiation stages of T-bet⁺ ILC1s. These cells were present across different organs and had the potential to mature toward CD127^intTCF-1^int and CD127⁻TCF-1⁻ ILC1s. Paralleling a gradual loss of TCF-1, differentiating ILC1s forfeited their expansion potential while increasing expression of effector molecules, reminiscent of T cell differentiation in secondary lymphoid organs. The transcription factor Hobit was induced in TCF-1^hi ILC1s and was required for their effector differentiation. These findings reveal sequential mechanisms of ILC1 lineage commitment and effector differentiation that are conserved across tissues. Our analyses suggest that ILC1s emerge as TCF-1^hi cells in the periphery and acquire a spectrum of organ-specific effector phenotypes through a uniform Hobit-dependent differentiation pathway driven by local cues.

Involved external institutions

Julius-Maximilians-Universität Würzburg

Germany (DE) University of Amsterdam

Netherlands (NL) Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics

Germany (DE) Roche Deutschland Holding GmbH

Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI)

Germany (DE)

How to cite

APA:

Friedrich, C., Taggenbrock, R.L.R.E., Doucet-Ladeveze, R., Golda, G., Moenius, R., Arampatzi, P.,... Gasteiger, G. (2021). Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues. Nature Immunology, 22(10), 1256-1267. https://doi.org/10.1038/s41590-021-01013-0

MLA:

Friedrich, Christin, et al. "Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues." Nature Immunology 22.10 (2021): 1256-1267.

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