T cells possess distinguishing effector functions and drive inflammatory disorders. We have previously identified IL-5–producing Th2 cells as the pathogenic population predominantly involved in the pathology of allergic inflammation. However, the cell-intrinsic signaling pathways that control the pathogenic Th2 cell function are still unclear. We herein report the high expression of acetyl-CoA carboxylase 1 (ACC1) in the pathogenic CD4+ T cell population in the lung and skin. The genetic deletion of CD4+ T cell–intrinsic ACC1 dampened eosinophilic and basophilic inflammation in the lung and skin by constraining IL-5 or IL-3 production. Mechanistically, ACC1-dependent fatty acid biosynthesis induces the pathogenic cytokine production of CD4+ T cells via metabolic reprogramming and the availability of acetyl-CoA for epigenetic regulation. We thus identified a distinct phenotype of the pathogenic T cell population in the lung and skin, and ACC1 was shown to be an essential regulator controlling the pathogenic function of these populations to promote type 2 inflammation.
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6 December 2021
Article|
November 23 2021
ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice
In Special Collection:
Immunology Update Winter 2022
Takahiro Nakajima
,
Takahiro Nakajima
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft)
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
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Toshio Kanno
,
Toshio Kanno
(Data curation, Formal analysis, Methodology, Software, Writing - original draft)
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
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Satoru Yokoyama
,
Satoru Yokoyama
(Investigation)
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
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Shigemi Sasamoto
,
Shigemi Sasamoto
(Investigation)
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
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Hikari K. Asou
,
Hikari K. Asou
(Investigation)
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
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Damon J. Tumes
,
Damon J. Tumes
2
Centre for Cancer Biology, University of South Australia, North Terrace, Adelaide, Australia
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Osamu Ohara
,
Osamu Ohara
(Data curation, Funding acquisition, Investigation, Methodology, Resources, Software, Supervision)
3
Department of Applied Genomics Kazusa DNA Research Institute, Chiba, Japan
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Toshinori Nakayama
,
Toshinori Nakayama
(Conceptualization, Supervision)
4
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
5AMED-CREST, AMED, Chiba, Japan
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Yusuke Endo
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
6
Department of Omics Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
Correspondence to Yusuke Endo: endo@kazusa.or.jp
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Takahiro Nakajima
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
Toshio Kanno
Data curation, Formal analysis, Methodology, Software, Writing - original draft
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
Satoru Yokoyama
Investigation
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
Shigemi Sasamoto
Investigation
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
Hikari K. Asou
Investigation
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
Damon J. Tumes
2
Centre for Cancer Biology, University of South Australia, North Terrace, Adelaide, Australia
Osamu Ohara
Data curation, Funding acquisition, Investigation, Methodology, Resources, Software, Supervision
3
Department of Applied Genomics Kazusa DNA Research Institute, Chiba, Japan
Toshinori Nakayama
Conceptualization, Supervision
4
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
5AMED-CREST, AMED, Chiba, Japan
Yusuke Endo
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
6
Department of Omics Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
Correspondence to Yusuke Endo: endo@kazusa.or.jp
Disclosures: The authors declare no competing interests exist.
Received:
March 22 2021
Revision Received:
September 12 2021
Accepted:
October 22 2021
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding
Funder(s):
Ministry of Education, Culture, Sports, Science and Technology
- Award Id(s): 18H04665,20H03455,20K21618,26221305,JP19H05650
Funder(s):
The Nakajima Foundation
Funder(s):
Terumo Foundation for Life Sciences and Arts
Funder(s):
Tokyo Biochemical Research Foundation
Funder(s):
Kato Memorial Bioscience Foundation
Funder(s):
Hamaguchi Foundation for the Advancement of Biochemistry
Funder(s):
Suzuken Memorial Foundation
Funder(s):
Kanae Foundation for the Promotion of Medical Science
Funder(s):
Takeda Science Foundation
Funder(s):
Mochida Memorial Foundation for Medical and Pharmaceutical Research
Funder(s):
GlaxoSmithKline Japan
- Award Id(s): 2019
Funder(s):
SENSHIN Medical Research Foundation
Funder(s):
Sumitomo Foundation
Funder(s):
Koyanagi Foundation
Funder(s):
Kishimoto Foundation 2019
Funder(s):
Uehara Memorial Foundation
Funder(s):
Nakatomi Foundation
Funder(s):
Research Foundation for Pharmaceutical Sciences Group A
Funder(s):
Cell Science Research Foundation
Funder(s):
Astellas Foundation for Research on Metabolic Disorders
Funder(s):
MSD Life Science Foundation, Public Interest Incorporated Foundation
Funder(s):
Nagase Science Technology Foundation
Funder(s):
Japan Agency for Medical Research and Development
- Award Id(s): JP21ek0410060
Funder(s):
AMED-CREST
- Award Id(s): JP21gm1210003
© 2021 Nakajima et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2021) 218 (12): e20210639.
Article history
Received:
March 22 2021
Revision Received:
September 12 2021
Accepted:
October 22 2021
Citation
Takahiro Nakajima, Toshio Kanno, Satoru Yokoyama, Shigemi Sasamoto, Hikari K. Asou, Damon J. Tumes, Osamu Ohara, Toshinori Nakayama, Yusuke Endo; ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice. J Exp Med 6 December 2021; 218 (12): e20210639. doi: https://doi.org/10.1084/jem.20210639
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