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

doi:10.1038/nature07240

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

ATP drives lamina propria TH17 cell differentiation

Atarashi, Koji, Nishimura, Junichi, Shima, Tatsuichiro, Umesaki, Yoshinori, Yamamoto, Masahiro, Onoue, Masaharu, Yagita, Hideo, Ishii, Naoto +3 more·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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Some but not all intestinal bacteria actively secrete ATP, and germ-free mice have lower gut ATP concentrations than controls.
“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
Germ-free mice show a severe reduction of TH17 lymphocytes in the colonic lamina propria, which can be rescued by direct ATP administration.
“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
Intraperitoneal injection of ATP exacerbated experimental colitis in mice.
“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
ATP elicits production of cytokines that favor TH17 differentiation by CD70high CD11clow antigen-presenting cells in the lamina propria.
“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
ATP, likely of commensal origin, contributes to conversion of naïve T cells into Th17 cells in the intestinal lamina propria.
“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]

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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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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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