ATP drives lamina propria TH17 cell differentiation
ATP drives lamina propria TH17 cell differentiation
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DOI：
10.1038/nature07240
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发表时间：
2008-10-09
期刊：
影响因子：
64.8
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Atarashi, Koji;Nishimura, Junichi;Takeda, Kiyoshi
产生IL-17的CD41T淋巴细胞(T(H)17细胞)构成T辅助细胞的一个亚群，参与宿主防御和几种免疫紊乱(1，2)。T(H)17细胞的一个耐人寻味的特征是它们选择性地和结构性地存在于肠道固有层(3)。在这里，我们展示了来自共生菌的三磷酸腺苷(ATP)可以激活固有层细胞的一个独特的亚群，CD70(高)CD11c(低)细胞，导致T(H)17细胞的分化。与无特定病原体的小鼠相比，无菌小鼠的腔内ATP浓度低得多，并伴有较少的固有层T(H)17细胞。给这些无菌小鼠全身或直肠注射三磷酸腺苷后，固有层T(H)17细胞的数量显著增加。固有层细胞的CD70(高)CD11c(低)亚群在ATP刺激下表达T(H)17倾向分子，如IL-6、IL-23p19和转化生长因子-β激活整合素-αV和-β8，并优先诱导共培养的初始CD4(+)T细胞分化为T(H)17。ATP的关键作用被进一步强调，观察到给药加剧了T细胞介导的结肠炎模型，增强了T(H)17的分化。这些观察结果强调了共生细菌和ATP对T(H)17在健康和疾病中分化的重要性，并解释了为什么T(H)17细胞特定地存在于肠道固有层。
Interleukin ( IL)- 17- producing CD4 1 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 trans-forming-growth- factor-beta-activating integrin-alpha V and -beta 8, 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.