美国霍华德休斯医学研究所Chrysothemis C. Brown小组开发出Thetis细胞的个体发生和转录调控。该研究于2026年2月3日发表于国际一流学术期刊《自然》杂志上。

在这里，课题组人员确定了一个RORγt⁺祖细胞群体，称为Thetis淋巴组织诱导祖细胞(TLP)，产生直接TC祖细胞（TCP）和淋巴组织诱导剂祖细胞（LTiP），并确定PU.1是控制TC命运的转录因子。尽管与髓源性传统树突状细胞（cDCs）的转录相似，但课题组人员发现TCs起源于共同淋巴样祖细胞（CLP）。浆细胞样DC（pDC）谱系决定转录因子TCF4的缺失扩展了TLPs和TCs，表明它们与pDC有共同的发育分支。TLPs在胎儿肝脏中富集；然而，与LTi细胞不同的是，TCs是在出生后出现的，这表明发育时的环境因素促进了TCP分化。该课题组发现了一个这样的线索-淋巴组织组织细胞提供RANKL——这是TC I分化所必需的。总之，这些发现定义了TC的个体发生和促进TC分化和异质性的转录因子，为未来研究这些神秘细胞及其在食物过敏和自身免疫耐受诱导方面的治疗潜力提供了便利。

据了解，Thetis细胞（TCs）是最近发现的一种RORγt⁺抗原呈递细胞谱系，包括其亚群，包括耐受性亚群TC IV，其指示对肠道微生物群和食物抗原的耐受性。生命早期的TCs发展浪潮为建立肠道耐受性创造了一个关键的机会窗口。然而，TCs的个体发生和形成其丰度和异质性的线索仍然未知，限制了利用其治疗潜力的努力。

附：英文原文

Title: Ontogeny and transcriptional regulation of Thetis cells

Author: Paucar Iza, Yoselin A., Park, Tyler, Baker, Eliyambuya, Shibu, Gayathri, Hoelting, Tilman, Feather, Greyson, Yadav, Anushka, Parisotto, Yollanda Franco, Zhao, Zihan, Akagbosu, Blossom, Bayes, Marc Elosua, Fisher, Logan, James, Lucas M., Ma, Jianping, Philpot, Benjamin D., Afzali, Behdad, Leslie, Christina, Brown, Chrysothemis C.

Issue&Volume: 2026-02-03

Abstract: Thetis cells (TCs) are a recently identified lineage of RORγt+ antigen-presenting cells comprising four subsets including a tolerogenic subset, TC IV, that instructs tolerance to gut microbiota and food antigens1–6. A developmental wave of TCs during early life creates a critical window of opportunity for establishing intestinal tolerance1,5. Yet the ontogeny of TCs and the cues shaping their abundance and heterogeneity remain unknown, limiting efforts to harness their therapeutic potential. Here we identify a population of RORγt+ progenitors, termed Thetis-Lymphoid Tissue inducer progenitors (TLP), that give rise to the immediate TC progenitor (TCP) and the Lymphoid Tissue inducer progenitor (LTiP), and identify PU.1 as the transcription factor governing TC fate. Despite transcriptional similarity to myeloid-derived conventional dendritic cells (cDCs), we show that TCs descend from the common lymphoid progenitor (CLP). Deletion of the plasmacytoid DC (pDC) lineage-determining transcription factor TCF4 expands TLPs and TCs, suggesting a shared developmental branch with pDCs. TLPs are enriched in fetal liver; however, unlike LTi cells, TCs emerge postnatally, pointing to developmentally-timed environmental cues that promote TCP differentiation. We identify one such cue–RANKL provision by lymphoid tissue organizer cells–which is essential for TC I differentiation. Together, these findings define the ontogeny of TCs and the transcription factors that promote TC differentiation and heterogeneity, facilitating future investigations of these enigmatic cells and their therapeutic potential for tolerance induction in food allergy and autoimmunity.

DOI: 10.1038/s41586-026-10198-z

Source: https://www.nature.com/articles/s41586-026-10198-z