Journal article

Deciphering the Innate Lymphoid Cell Transcriptional Program

Cyril Seillet, Lisa A Mielke, Daniela B Amann-Zalcenstein, Shian Su, Jerry Gao, Francisca F Almeida, Wei Shi, Matthew E Ritchie, Shalin H Naik, Nicholas D Huntington, Sebastian Carotta, Gabrielle T Belz

Cell Reports | CELL PRESS | Published : 2016

Abstract

Innate lymphoid cells (ILCs) are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF+ ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. Importantly, induction of ILC lineage commitment required only transient expr..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Funding Acknowledgements

We thank A. Sharpe (Harvard Medical School) and D. Gray (WEHI) for providing Pcdc1<SUP>-/-</SUP> mice, H. Morse III (NIH) and H. Wang (NIH) for providing the Irf8<SUP>egfp</SUP> mice, and S.L. Nutt for providing PU.1<SUP>gfp</SUP> mice for analyses. We thank S.L. Nutt and M. Chopin for helpful discussions and critical review of the manuscript. We are indebted to the facilities of our institute, particularly those responsible for animal husbandry and flow cytometry. N.D.H is a recipient of a melanoma research grant from the Harry J. Lloyd Charitable Trust. G.T.B. is supported by an Australian Research Council Future Fellowship. W.S. is supported by a Centenary Fellowship from the Commonwealth Serum Laboratory, Australia. This work was supported by project grants GNT1027472, 1049407, 1047903, and 1062820 (to G.T.B., N.D.H. and S.H.N.) of the National Health and Medical Research Council (NHMRC) of Australia, The Rebecca L. Cooper Medical Foundation, Victorian State Government Operational Infrastructure Support, and the Australian Government NHMRC IRIIS. S.C. is an employee of Boehringer-Ingelheim.