Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Innate lymphoid cells (ILCs) are tissue-resident effector cells with roles in tissue homeostasis, protective immunity, and inflammatory disease. Group 3 ILCs (ILC3s) are classically defined by the master transcription factor RORγt. However, ILC3 can be further subdivided into subsets that share type 3 effector modules that exhibit significant ontological, transcriptional, phenotypic, and functional heterogeneity. Notably lymphoid tissue inducer (LTi)-like ILC3s mediate effector functions not typically associated with other RORγt-expressing lymphocytes, suggesting that additional transcription factors contribute to dictate ILC3 subset phenotypes. Here, we identify Bcl6 as a subset-defining transcription factor of LTi-like ILC3s in mice and humans. Deletion of Bcl6 results in dysregulation of the LTi-like ILC3 transcriptional program and markedly enhances expression of interleukin-17A (IL-17A) and IL-17F in LTi-like ILC3s in a manner in part dependent upon the commensal microbiota-and associated with worsened inflammation in a model of colitis. Together, these findings redefine our understanding of ILC3 subset biology.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 11 vom: 28. Nov., Seite 113425 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tachó-Piñot, Roser [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.12.2023 Date Revised 06.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.113425 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36442527X |
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| 245 | 1 | 0 | |a Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3 |
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| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Innate lymphoid cells (ILCs) are tissue-resident effector cells with roles in tissue homeostasis, protective immunity, and inflammatory disease. Group 3 ILCs (ILC3s) are classically defined by the master transcription factor RORγt. However, ILC3 can be further subdivided into subsets that share type 3 effector modules that exhibit significant ontological, transcriptional, phenotypic, and functional heterogeneity. Notably lymphoid tissue inducer (LTi)-like ILC3s mediate effector functions not typically associated with other RORγt-expressing lymphocytes, suggesting that additional transcription factors contribute to dictate ILC3 subset phenotypes. Here, we identify Bcl6 as a subset-defining transcription factor of LTi-like ILC3s in mice and humans. Deletion of Bcl6 results in dysregulation of the LTi-like ILC3 transcriptional program and markedly enhances expression of interleukin-17A (IL-17A) and IL-17F in LTi-like ILC3s in a manner in part dependent upon the commensal microbiota-and associated with worsened inflammation in a model of colitis. Together, these findings redefine our understanding of ILC3 subset biology | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Bcl6 | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a IL-17 | |
| 650 | 4 | |a ILC3 | |
| 650 | 4 | |a innate lymphoid cells | |
| 650 | 4 | |a intestinal immunity | |
| 650 | 4 | |a lymphoid tissue inducer | |
| 650 | 4 | |a microbiota | |
| 650 | 4 | |a transcription factor | |
| 650 | 7 | |a Bcl6 protein, mouse |2 NLM | |
| 650 | 7 | |a Nuclear Receptor Subfamily 1, Group F, Member 3 |2 NLM | |
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| 650 | 7 | |a BCL6 protein, human |2 NLM | |
| 700 | 1 | |a Stamper, Christopher T |e verfasserin |4 aut | |
| 700 | 1 | |a King, James I |e verfasserin |4 aut | |
| 700 | 1 | |a Matei-Rascu, Veronika |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, Erin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Roberts, Luke B |e verfasserin |4 aut | |
| 700 | 1 | |a Bassett, John W |e verfasserin |4 aut | |
| 700 | 1 | |a Melo-Gonzalez, Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Fiancette, Rémi |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, I-Hsuan |e verfasserin |4 aut | |
| 700 | 1 | |a Dent, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Harada, Yohsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Finlay, Conor |e verfasserin |4 aut | |
| 700 | 1 | |a Mjösberg, Jenny |e verfasserin |4 aut | |
| 700 | 1 | |a Withers, David R |e verfasserin |4 aut | |
| 700 | 1 | |a Hepworth, Matthew R |e verfasserin |4 aut | |
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