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Cited by 334IL-33, ST2, and ILC PathwaysT-cell and B-cell ImmunologyGenomics and Chromatin Dynamics

Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality

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Shih, Han-Yu, Sciumè, Giuseppe, Mikami, Yohei, Guo, Liying, Sun, Hong-Wei, Brooks, Stephen R., Urban, Joseph F., Davis, Fred P. +2 more·2016·Cell
DOI 10.1016/j.cell.2016.04.029PMC PMC4874839
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Abstract

Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis and mirror adaptive CD4(+) T helper (Th) cell subtypes in both usage of effector molecules and transcription factors. To better understand the relationship between ILC subsets and their Th cell counterparts, we measured genome-wide chromatin accessibility. We find that chromatin in proximity to effector genes is selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions is acquired in a stepwise manner during development and changes little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurs in naive CD4(+) T cells during Th cell differentiation using a type-2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways.

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  • The innate lymphoid cell developmental program appears to resemble the intrathymic T-cell program in many respects.

    “So far the innate lymphoid cell developmental program in particular appears to resemble the intrathymic T-cell program in many respects (154–157), enough to raise the question of what makes T-cell precursors wait to activate genes like Tcf7 and Gata3 until they reach the thymus.”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [154]

    The Discussion section, “T cells and ILCs: Regulomes Converge following Infection” (page not provided), describes a “reasonably clear distinction” between ILC and T-cell development. The paper reports shared transcription factors and convergence of their regulomes after infection, but distinguishes those similarities from a resemblance between their developmental programs. (LLM, conf=0.83)

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Authors
Shih, H.-Y., Sciumè, G., Mikami, Y., Guo, L., Sun, H.-W., Brooks, S. R., Urban, J. F., Davis, F. P., Kanno, Y., & O’Shea, J. J.
Affiliations
  • National Institutes of Health (US)
  • Agricultural Research Service (US)
Corresponding author
  • Shih, Han-Yu
  • O’Shea, John J.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2016-05
Volume
165
Issue
5
Pages
1120-1133
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2016.04.029
PMC
PMC4874839
OpenAlex
W2345615811
Cited by
334
References
62
Citations by year
2026: 21 · 2025: 24 · 2024: 26 · 2023: 30 · 2022: 33 · 2021: 37 · 2020: 35 · 2019: 42 · 2018: 40 · 2017: 31 · 2016: 14 · 2014: 1
FWCI
25.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIAAR041159)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
innate lymphoid cells, ILC2, CD4+ T helper cells, Th2 cells, chromatin accessibility, regulome, developmental gene regulation, chromatin remodeling, transcription factors, effector genes, innate-adaptive immune crosstalk, naive T cells
MeSH terms
Animals, Female, Gene Expression Regulation, Lymphocytes, Mice, Inbred C57BL, Cell Lineage, Mice, Gene Regulatory Networks, Transcriptome

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