TSLP将肠道营养感知与ILC2簇细胞回路的扩增联系起来，这一成果由加州大学Richard M. Locksley课题组经过不懈努力而取得。该研究于2025年11月12日发表于国际一流学术期刊《自然—免疫学》杂志上。

在这里，该研究团队发现胸腺基质淋巴生成素(TSLP) -一种与ILC2激活有关的细胞因子-在上皮下成纤维细胞中组成性地表达，包括远端细胞和隐窝相关的滋养细胞，它们是维持上皮身份所必需的特化成纤维细胞。饲喂增加TSLP，诱导ILC2型2种细胞因子通过删除成纤维细胞中的TSLP或ILC2s上的TSLP受体而减弱。小鼠和人肠成纤维细胞都表达胰高血糖素样肽-2（GLP-2）受体，胰高血糖素样肽-2是肠内分泌细胞在食物摄入后释放的一种肠营养生长因子。GLP-2促进小鼠和人肠成纤维细胞的肠道TSLP，以及TSLP依赖性ILC2激活和小鼠簇状细胞增生，它们将营养检测与ILC2介导的簇状细胞化学感觉回路扩增联系起来，从而促进上皮对摄入货物的监视。

据了解，组先天性淋巴细胞（ILC2s）在小肠中普遍存在，但其在体内平衡中的作用尚不清楚。

附：英文原文

Title: TSLP links intestinal nutrient sensing with amplification of the ILC2–tuft cell circuit

Author: Liao, Chang, Mennillo, Elvira, Kattah, Michael G., Ji, Ming, Wang, Zhi-En, Drucker, Daniel J., Liang, Hong-Erh, Locksley, Richard M.

Issue&Volume: 2025-11-12

Abstract: Group2 innate lymphocytes (ILC2s) are prevalent in small intestine but their role during homeostasis is unclear. Here we show that thymic stromal lymphopoietin (TSLP)—a cytokine implicated in ILC2 activation—is expressed constitutively in subepithelial fibroblasts, including telocytes and crypt-associated trophocytes, which are specialized fibroblasts necessary to sustain epithelial identity. Feeding increases TSLP and induces ILC2 type2 cytokines that are attenuated by deletion of TSLP in fibroblasts or TSLP receptor on ILC2s. Both mouse and human intestinal fibroblasts express receptors for glucagon-like peptide-2 (GLP-2)—an intestinotrophic growth factor released by enteroendocrine cells following food intake. GLP-2 promotes intestinal TSLP in mouse and human intestinal fibroblasts, and TSLP-dependent ILC2 activation and tuft cell hyperplasia in mice, thus linking nutrient detection with ILC2-mediated amplification of the tuft cell chemosensory circuit that promotes epithelial surveillance of ingested cargo.

DOI: 10.1038/s41590-025-02328-y

Source: https://www.nature.com/articles/s41590-025-02328-y