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Updated: May 4, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Published on: September 27, 2013

ATP drives lamina propria T(H)17 cell differentiation.

Koji Atarashi¹, Junichi Nishimura, Tatsuichiro Shima

¹Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

|August 22, 2008

Summary

Commensal bacteria-derived adenosine triphosphate (ATP) activates specific intestinal cells, promoting the differentiation of T helper 17 (T(H)17) cells. This explains T(H)17 cell presence in the gut and their role in immune disorders.

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Area of Science:

Immunology
Microbiology
Gastroenterology

Background:

T helper 17 (T(H)17) cells are crucial for host defense and immune disorders.
T(H)17 cells are uniquely and constitutively present in the intestinal lamina propria.

Purpose of the Study:

To investigate the role of adenosine triphosphate (ATP) in T(H)17 cell differentiation in the intestinal lamina propria.
To elucidate the mechanism by which commensal bacteria influence T(H)17 cell populations.

Main Methods:

Comparison of T(H)17 cell numbers and ATP concentrations in germ-free versus specific-pathogen-free mice.
Administration of ATP to germ-free mice to assess its effect on T(H)17 cell differentiation.
Analysis of specific lamina propria cell subsets (CD70(high)CD11c(low)) for T(H)17-prone molecule expression.
Assessment of ATP's impact on a T-cell-mediated colitis model.

Main Results:

Germ-free mice have significantly lower luminal ATP and fewer lamina propria T(H)17 cells compared to SPF mice.
ATP administration to germ-free mice markedly increased lamina propria T(H)17 cell numbers.
A specific subset of lamina propria cells (CD70(high)CD11c(low)) responded to ATP by expressing T(H)17-promoting molecules and inducing T(H)17 differentiation.
ATP administration exacerbated T-cell-mediated colitis, correlating with enhanced T(H)17 differentiation.

Conclusions:

Commensal bacteria-derived ATP is a key factor driving T(H)17 cell differentiation in the intestinal lamina propria.
This mechanism explains the specific localization and abundance of T(H)17 cells in the gut.
ATP's role in T(H)17 differentiation has implications for understanding and treating immune-mediated intestinal diseases.