The DOI matches its Crossref record; 119 of the 122 references it cites were found in a registry or an index.
The chromatin landscape of Th17 cells reveals mechanisms of diversification of regulatory and pro-inflammatory states
Open accessAbstract
Th17 cells are a heterogenous cell population consisting of non-pathogenic Th17 cells (npTh17) that contribute to tissue homeostasis and pathogenic Th17 cells (pTh17) that are potent mediators of tissue inflammation. To reveal regulatory mechanisms underlying Th17 heterogeneity, we performed combined ATAC-seq and RNA-seq and discovered substantial differences in the chromatin landscape of npTh17 and pTh17 cells both in vitro and in vivo . Compared to other CD4 + T cell subsets, npTh17 cells share accessible chromatin programs with T regs , and pTh17 cells have an intermediate profile spanning features of npTh17 cells and Th1 cells. Integrating single-cell ATAC-seq and single-cell RNA-seq, we inferred self-reinforcing and mutually exclusive regulatory networks controlling the different cell states and predicted transcription factors (TFs) shaping the chromatin landscape of Th17 cell pathogenicity. We validated one novel TF, BACH2, which promotes immunomodulatory npTh17 programs and restrains pro-inflammatory Th1-like programs in Th17 cells and showed genetic evidence for protective variants in the human BACH2 locus associated with multiple sclerosis. Our work uncovered mechanisms that regulate Th17 heterogeneity, revealed shared regulatory programs with other CD4 + T cell subsets, and identified novel drivers of Th17 pathogenicity as potential targets to mitigate autoimmunity.
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In the citing paper
“analysis of Th17 cells in different tissue sites has revealed that Th17 cells may exhibit distinct transcriptional profiles associated with either homeostatic or pathogenic functions”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“we profiled Th17 cells from multiple tissues of naïve IL-17-fate reporter mice by single-cell RNA-seq”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“tissue Th17 cells were found to exhibit tissue-specific transcriptomic signatures”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Under inflammatory conditions, tissue Th17 cells have been reported to exhibit plastic changes in their effector programs.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Use of cell fate reporter mice showed that T cells that initially express IL-17 (ex-Th17 cells) can subsequently express proinflammatory cytokines, including IFNγ and GM-CSF [38, 76].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“We identified IL-23-signaling as a main driver of the conversion of homeostatic IL-17A/F+ SLAMF6+ cells to pathogenic IFNγ+ GM-CSF+ CXCR6+ cells in EAE [38].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Hence, we propose GM-CSF expression as part of a general pathogenic program together with other pro-inflammatory molecules such as BHLHE40, IFNγ, and CXCR6 that can be induced across multiple T helper cell subsets [33, 38, 177].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“A recent study from one of our laboratories, using fate reporter mice, provides strong in vivo support for the notion that homeostatic Th17 cells differentiate into inflammatory Th17 cells that mediate autoimmune disease.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
In the citing paper
“Using single cell genomics, we identified a homeostatic IL-17A/F+ population, marked by SLAMF6, that gives rise to a pathogenic IFNγ+ GM-CSF+ population marked by CXCR6 during EAE [38], suggesting a direct in vivo relationship between these cells.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [38]
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Research works printed but not linked: 1
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TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286
Self-citationTh17 cell pathogenicity in autoimmune disease
Park, E., & Ciofani, M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01535-9 · Cited by 75
Hu, Y., Yang, Y., Li, Y., Zhang, Q., Zhang, W., Jia, J., Han, Z., & Wang, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1651063 · Cited by 74
IL-17: Balancing Protective Immunity and Pathogenesis
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Metadata
- Authors
- Thakore, P. I., Schnell, A., Zhao, M., Huang, L., Hou, Y., Christian, E., Zaghouani, S., Wang, C., Singh, V., Ma, S., Sankar, V., Notarbartolo, S., Buenrostro, J. D., Sallusto, F., Patsopoulos, N. A., Rozenblatt-Rosen, O., Kuchroo, V. K., & Regev, A.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- ETH Zurich (CH)
- Corresponding author
- Kuchroo, Vijay K.
- Regev, Aviv
- ORCID
- Venue
- Nature Immunology
- Publisher
- openRxiv
- Published
- 2022-02-26
- Volume
- 25
- Issue
- 8
- Pages
- 1395-1410
- ISSN
- 1529-2908 (ISSN-L)
- OpenAlex
- W4400657378
- Cited by
- 57
- References
- 122
- Citations by year
- 2026: 24 · 2025: 24 · 2024: 4 · 2023: 5
- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Nature Immunology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Department of Health and Human Services (R01AI144166, R01NS30843, R01NS045937)
- National Institutes of Health (R01NS30843)
- National Institute of Allergy and Infectious Diseases (R01AI144166)
- National Institute of Neurological Disorders and Stroke (R01NS030843, R01NS045937)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- 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
- BACH2, Th17 cells, chromatin accessibility, regulatory T cells, transcriptional regulatory networks, IL-17, multiple sclerosis, autoimmunity, epigenetic regulation, cellular heterogeneity
- MeSH terms
- Animals, Chromatin, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Inflammation, Mice, Inbred C57BL, Multiple Sclerosis, Mice, Knockout, Th1 Cells, T-Lymphocytes, Regulatory, Basic-Leucine Zipper Transcription Factors, Mice, Th17 Cells, Single-Cell Analysis
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- CoChat. (2026). Citation check: The chromatin landscape of Th17 cells reveals mechanisms of diversification of regulatory and pro-inflammatory states. https://app.cochat.ai/papers/10.1101/2022.02.26.482041
- The paper
- Thakore, P. I., Schnell, A., Zhao, M., Huang, L., Hou, Y., Christian, E., Zaghouani, S., Wang, C., Singh, V., Ma, S., Sankar, V., Notarbartolo, S., Buenrostro, J. D., Sallusto, F., Patsopoulos, N. A., Rozenblatt-Rosen, O., Kuchroo, V. K., & Regev, A. (2022). The chromatin landscape of Th17 cells reveals mechanisms of diversification of regulatory and pro-inflammatory states. Nature Immunology. https://doi.org/10.1101/2022.02.26.482041
