학술논문
Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues
innate lymphoid cells
innate lymphoid cells
Document Type
Report
Author
Source
Nature Immunology. October 2021, Vol. 22 Issue 10, p1256, 12 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Christin Friedrich [sup.1] , Renske L. R. E. Taggenbrock [sup.2] , Rémi Doucet-Ladevèze [sup.1] , Gosia Golda [sup.3] [sup.4] [sup.5] , Rebekka Moenius [sup.1] , Panagiota Arampatzi [sup.6] , [...]
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.sup.+CD127.sup.hiTCF-1.sup.hi early differentiation stages of T-bet.sup.+ ILC1s. These cells were present across different organs and had the potential to mature toward CD127.sup.intTCF-1.sup.int and CD127.sup.-TCF-1.sup.- 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.sup.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.sup.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. ILCs are considered preformed effector cells. Gasteiger and colleagues report that ILC1s undergo effector differentiation after lineage commitment. Hobit.sup.+ ILC1s emerge as cKit.sup.+TCF-1.sup.hi cells that generate tissue-specific helper- and cytotoxic-like cells along a Hobit-dependent trajectory.
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.sup.+CD127.sup.hiTCF-1.sup.hi early differentiation stages of T-bet.sup.+ ILC1s. These cells were present across different organs and had the potential to mature toward CD127.sup.intTCF-1.sup.int and CD127.sup.-TCF-1.sup.- 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.sup.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.sup.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. ILCs are considered preformed effector cells. Gasteiger and colleagues report that ILC1s undergo effector differentiation after lineage commitment. Hobit.sup.+ ILC1s emerge as cKit.sup.+TCF-1.sup.hi cells that generate tissue-specific helper- and cytotoxic-like cells along a Hobit-dependent trajectory.