The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
ATP drives lamina propria TH17 cell differentiation
Abstract
Interleukin (IL)-17-producing CD4(+) T lymphocytes (T(H)17 cells) constitute a subset of T-helper cells involved in host defence and several immune disorders. An intriguing feature of T(H)17 cells is their selective and constitutive presence in the intestinal lamina propria. Here we show that adenosine 5'-triphosphate (ATP) that can be derived from commensal bacteria activates a unique subset of lamina propria cells, CD70(high)CD11c(low) cells, leading to the differentiation of T(H)17 cells. Germ-free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to specific-pathogen-free mice. Systemic or rectal administration of ATP into these germ-free mice results in a marked increase in the number of lamina propria T(H)17 cells. A CD70(high)CD11c(low) subset of the lamina propria cells expresses T(H)17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor-beta-activating integrin-alphaV and -beta8, in response to ATP stimulation, and preferentially induces T(H)17 differentiation of co-cultured naive CD4(+) T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T-cell-mediated colitis model with enhanced T(H)17 differentiation. These observations highlight the importance of commensal bacteria and ATP for T(H)17 differentiation in health and disease, and offer an explanation of why T(H)17 cells specifically present in the intestinal lamina propria.
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In the citing paper
“some, but not all, intestinal bacteria actively secrete ATP, and germ-free mice have lower ATP concentrations in their gut than controls (Atarashi et al., 2008; Hironaka et al., 2013; Iwase et al., 2010).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Atarashi et al., 2008
In the citing paper
“Germ-free mice show a severe reduction of TH17 lymphocytes in the lamina propria of the colonic epithelium, which can be rescued by the direct administration of ATP.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Atarashi et al., 2008
In the citing paper
“intraperitoneal injection of ATP exacerbated experimental colitis in mice (Atarashi et al., 2008).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Atarashi et al., 2008
In the citing paper
“Specifically, ATP elicits the production of cytokines that favor TH17 differentiation by CD70high CD11clow antigen-presenting cells (APCs) in the lamina propria (Atarashi et al., 2008).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Atarashi et al., 2008
In the citing paper
“ATP, likely of commensal origin, contributes to the conversion of naïve T cells into Th17 in the intestinal LP [30].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [30]
Citations
Cites
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Transforming growth factor-β induces development of the TH17 lineage
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Molecular Physiology of P2X Receptors
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The gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Gut microbiota in health and disease
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Human nutrition, the gut microbiome and the immune system
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Metadata
- Authors
- Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., & Takeda, K.
- Affiliations
- The University of Osaka (JP)
- Yakult Central Institute (JP)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Tohoku University (JP)
- University of Leicester (GB)
- Corresponding author
- Honda, Kenya
- Takeda, Kiyoshi
- ORCID
- Venue
- Nature
- Published
- 2008-08-20
- Volume
- 455
- Issue
- 7214
- Pages
- 808-812
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2051529467
- Cited by
- 1,089
- References
- 33
- Citations by year
- 2026: 19 · 2025: 37 · 2024: 51 · 2023: 34 · 2022: 39 · 2021: 49 · 2020: 52 · 2019: 56 · 2018: 54 · 2017: 54 · 2016: 64 · 2015: 72 · 2014: 81 · 2013: 78 · 2012: 71
- FWCI
- 38.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- Th17 cell differentiation, ATP, intestinal lamina propria, commensal bacteria, intestinal dendritic cells, IL-17, interleukin-6, TGF-beta, germ-free mice, T cell-mediated colitis, inflammatory bowel disease, innate immunity
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Differentiation, Cells, Cultured, Colitis, Disease Models, Animal, Feces, Female, Germ-Free Life, T-Lymphocytes, Helper-Inducer, Immunoglobulin A, Male, Mucous Membrane, Receptors, Purinergic P2, Interleukin-17, CD11c Antigen, Mice, CD27 Ligand
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