Open AccessEffector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues
Author(s) -
Chr. Friedrich,
Renske Taggenbrock,
Rémi DoucetLadevèze,
Gosia Golda,
Rebekka Moenius,
Panagiota Arampatzi,
Natasja A. M. Kragten,
Katharina Kreymborg,
Mercedes Gomez de Agüero,
Wolfgang Kastenmüller,
AntoineEmmanuel Saliba,
Dominic Grün,
Klaas P.J.M. van Gisbergen,
Georg Gasteiger
Publication year - 2021
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-021-01013-0
Subject(s) - effector , biology , interleukin 7 receptor , innate lymphoid cell , microbiology and biotechnology , transcription factor , cellular differentiation , lineage (genetic) , immunology , innate immune system , t cell , genetics , immune system , gene , il 2 receptor
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 hi TCF-1 hi early differentiation stages of T-bet + ILC1s. These cells were present across different organs and had the potential to mature toward CD127 int TCF-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.