Cited by 1,089Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyInflammatory Bowel Disease

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ATP drives lamina propria TH17 cell differentiation

Atarashi, Koji, Nishimura, Junichi, Shima, Tatsuichiro, Umesaki, Yoshinori, Yamamoto, Masahiro, Onoue, Masaharu, Yagita, Hideo, Ishii, Naoto, Evans, Richard, Honda, Kenya, Takeda, Kiyoshi·2008·Nature

DOI 10.1038/nature07240

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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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“For instance, intraperitoneal injection of ATP exacerbated experimental colitis in mice (Atarashi et al., 2008).”
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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: Atarashi, Koji
Nishimura, Junichi
Umesaki, Yoshinori
Yamamoto, Masahiro
Ishii, Naoto
Evans, Richard
Honda, Kenya
Takeda, Kiyoshi
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2008-08-20
Volume: 455
Issue: 7214
Pages: 808-812
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07240
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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ATP drives lamina propria TH17 cell differentiation

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