美国圣犹达儿童研究医院Laura K. Mackay和澳大利亚墨尔本大学Maximilien Evrard共同合作，近期取得重要工作进展。他们研究提出，视黄酸和TGF-β协调器官特异性组织驻留程序。相关研究成果2024年10月14日在线发表于《免疫》杂志上。

据介绍，组织驻留记忆T（T_RM）细胞是组织免疫不可或缺的一部分，它们存在于不同的解剖部位，并遵循共同的转录框架。这些细胞如何整合不同的局部线索以采用共同的T_RM细胞命运仍然知之甚少。

研究人员表明，尽管皮肤T_RM细胞严格需要转化生长因子β（TGF-β）进行组织驻留，但其他部位的T_RM细胞利用代谢物视黄酸（RA）来驱动另一种分化途径，在肝脏中指导TGF-β非依赖性组织驻留程序，并与TGF-β协同驱动小肠中的T_RM细胞。RA是肠道T_RM人群长期维持所必需的，部分原因是阻碍了他们的逆行。

此外，增强的RA信号调节了T_RM细胞的表型和功能，这一现象反映在微生物多样性增加的小鼠身上。

总之，这一研究揭示了RA是指导组织免疫监测的宿主-环境相互作用的基本组成部分。

附：英文原文

Title: Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency

Author: Andreas Obers, Tobias Poch, Grace Rodrigues, Susan N. Christo, Luke C. Gandolfo, Raissa Fonseca, Ali Zaid, Joey En Yu Kuai, Hongjin Lai, Pirooz Zareie, Marina H. Yakou, Lachlan Dryburgh, Thomas N. Burn, James Dosser, Frank A. Buquicchio, Caleb A. Lareau, Calum Walsh, Louise Judd, Maria Rafailia Theodorou, Katharina Gutbrod, Peter Drmann, Jenny Kingham, Tim Stinear, Axel Kallies, Jan Schroeder, Scott N. Mueller, Simone L. Park, Terence P. Speed, Ansuman T. Satpathy, Tri Giang Phan, Christoph Wilhelm, Colby Zaph, Maximilien Evrard, Laura K. Mackay

Issue&Volume: 2024-10-14

Abstract: Tissue-resident memory T (TRM) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common TRM cell fate remains poorly understood. Here, we show that whereas skin TRM cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive TRM cells in the small intestine. We found that RA was required for the long-term maintenance of intestinal TRM populations, in part by impeding their retrograde migration. Moreover, enhanced RA signaling modulated TRM cell phenotype and function, a phenomenon mirrored in mice with increased microbial diversity. Together, our findings reveal RA as a fundamental component of the host-environment interaction that directs immunosurveillance in tissues.

DOI: 10.1016/j.immuni.2024.09.015

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00459-X