Journal Article

ATP drives lamina propria TH17 cell differentiation

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

2008

Overview

Bacterial ATP helps T H 17 cells The intestinal lamina propria, a layer of cells forming part of the mucous membrane, boasts a complicated mix of cell populations, including the selective presence of T H 17 or T helper 17 cells, the subset of T helpers that produces interleukin 17. A study in mice now shows that commensal bacteria activate a unique subset of intestinal dendritic cells to induce interleukin-6 production and TGF- beta activation, thereby promoting the local differentiation of T H 17 cells. It is the ATP that the bacteria produce that promotes this effect. This finding highlights the importance of commensal bacteria and ATP in immuno-logical diseases, and may help in determining the mechanisms by which aberrant T H 17 cell responses result in immune disorders including inflammatory bowel diseases. 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 1 , 2 . An intriguing feature of T H 17 cells is their selective and constitutive presence in the intestinal lamina propria 3 . 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-β-activating integrin-αV and -β8, 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.

• Publisher: Nature Publishing Group UK,Nature Publishing
• Subject: Biological and medical sciences / Cell differentiation, maturation, development, hematopoiesis / Cell physiology / Fundamental and applied biological sciences. Psychology / Humanities and Social Sciences / letter / Molecular and cellular biology / multidisciplinary / Science / Science (multidisciplinary)