Nutrient-derived signals regulate eosinophil adaptation to the small intestine.
Nutrient-derived signals regulate eosinophil adaptation to the small intestine.
复制标题
营养源性信号调节嗜酸性粒细胞对小肠的适应。
DOI：
10.1073/pnas.2316446121
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发表时间：
2024-01-30
影响因子：
11.1
通讯作者：
Medzhitov, Ruslan
中科院分区：
文献类型：
--
作者：
Kutyavin, Vassily I.;Korn, Lisa L.;Medzhitov, Ruslan
除了保护宿主免受病原微生物的侵害外，免疫细胞还执行需要组织特异性适应的非经典生理功能。嗜酸性粒细胞是在营养丰富的小肠（SI）中特别丰富的免疫细胞，但营养物质是否指导它们适应该组织在很大程度上尚未探索。在这项研究中，我们发现，嗜酸性粒细胞逐渐迁移沿着隐窝绒毛轴和发展成为一个转录不同的绒毛居民亚群。我们确定这种适应依赖于维生素A的代谢产物视黄酸。此外，我们意外地发现，高水平的膳食氨基酸限制绒毛驻地嗜酸性粒细胞的积累，加速嗜酸性粒细胞的周转。这项研究强调了膳食营养素在塑造SI免疫细胞群体中的重要作用。嗜酸性粒细胞被公认为2型免疫的效应细胞，但它们也在稳态条件下在许多组织中积累。然而，支配稳态嗜酸性粒细胞积累和组织特异性适应的过程及其功能意义仍然不清楚。在这里，我们研究了嗜酸性粒细胞如何适应小肠（SI）微环境和调节这一过程的局部信号。我们观察到，嗜酸性粒细胞逐渐迁移沿着隐窝绒毛轴，从而产生一个绒毛居民亚群与一个独特的转录签名。维甲酸信号是维持该亚群所必需的，而IL-5在很大程度上超出了其在嗜酸性粒细胞产生中的典型作用。令人惊讶的是，我们发现高蛋白饮食抑制绒毛驻留嗜酸性粒细胞的积累。纯化的氨基酸足以产生这种效应，这是组织微环境中嗜酸性粒细胞周转加速的结果，而不是由于骨髓中发育的改变。我们的研究提供了深入了解嗜酸性粒细胞适应SI的过程，强调其对营养来源的信号的依赖。
In addition to protecting the host from pathogenic microbes, immune cells perform noncanonical physiological functions which require tissue-specific adaptation. Eosinophils are immune cells that are particularly abundant in the nutrient-rich small intestine (SI), but whether nutrients guide their adaptation to this tissue is largely unexplored. In this study, we found that eosinophils gradually migrate along the crypt–villus axis and develop into a transcriptionally distinct villus-resident subpopulation. We determined that this adaptation depends on retinoic acid, a metabolite of vitamin A. Furthermore, we unexpectedly found that high levels of dietary amino acids limit the accumulation of villus-resident eosinophils by accelerating eosinophil turnover. This study highlights the important role of dietary nutrients in shaping the immune cell populations of the SI. Eosinophils are well recognized as effector cells of type 2 immunity, yet they also accumulate in many tissues under homeostatic conditions. However, the processes that govern homeostatic eosinophil accumulation and tissue-specific adaptation, and their functional significance, remain poorly defined. Here, we investigated how eosinophils adapt to the small intestine (SI) microenvironment and the local signals that regulate this process. We observed that eosinophils gradually migrate along the crypt–villus axis, giving rise to a villus-resident subpopulation with a distinct transcriptional signature. Retinoic acid signaling was specifically required for maintenance of this subpopulation, while IL-5 was largely dispensable outside of its canonical role in eosinophil production. Surprisingly, we found that a high-protein diet suppressed the accumulation of villus-resident eosinophils. Purified amino acids were sufficient for this effect, which was a consequence of accelerated eosinophil turnover within the tissue microenvironment and was not due to altered development in the bone marrow. Our study provides insight into the process of eosinophil adaptation to the SI, highlighting its reliance on nutrient-derived signals.
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影响因子：
24.8
作者：
Cosway EJ;White AJ;Parnell SM;Schweighoffer E;Jolin HE;Bacon A;Rodewald HR;Tybulewicz V;McKenzie ANJ;Jenkinson WE;Anderson G
通讯作者：
Anderson G
影响因子：
30.3
作者：
Cao, Y. Grace;Bae, Sena;Villarreal, Jannely;Moy, Madelyn;Chun, Eunyoung;Michaud, Monia;Lang, Jessica K.;Glickman, Jonathan N.;Lobel, Lior;Garrett, Wendy S.
通讯作者：
Garrett, Wendy S.
影响因子：
--
作者：
ERICKSON, RH;SUZUKI, Y;KIM, YS
通讯作者：
KIM, YS
DOI：
10.1073/pnas.1304046110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Goh, Y. P. Sharon;Henderson, Neil C.;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
--
作者：
Germain, Pierre;Gaudon, Claudine;Gronemeyer, Hinrich
通讯作者：
Gronemeyer, Hinrich