Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Mucosal Immunol. 2012 Mar;5(2):184-93. doi: 10.1038/mi.2011.64. Epub 2012 Jan 11.
Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and keratinocytes, and is involved in immune homeostasis or inflammation. The mechanism through which TSLP regulates intestinal inflammation is unclear. Here, we report that mouse dendritic cells (DCs) express TSLP both in vitro and in vivo in response to Toll-like receptor ligation in a MyD88-dependent fashion. TSLP is produced by the CD103(+) subset of tolerogenic gut DCs and is downregulated during experimental colitis. TSLP produced by DCs acts directly on T cells by reducing their capacity to produce interleukin (IL)-17 and fostering the development of Foxp3(+) T cells. Consistently, TSLP protects against colitis development through a direct action on T cells, as adoptive transfer of naïve T cells from TSLPR(-/-) to SCID mice results in a more severe colitis, with increased frequency of IL-17-producing T cells and inflammatory cytokines. Hence, we describe a new anti-inflammatory role of TSLP in the gut.
胸腺基质淋巴细胞生成素（TSLP）由上皮细胞和角质形成细胞产生，并参与免疫稳态或炎症反应。TSLP 调节肠道炎症的机制尚不清楚。在这里，我们报告说，在体外和体内，在 TLR 配体交联时，鼠树突状细胞（DC）以 MyD88 依赖性的方式表达 TSLP。TSLP 由耐受型肠道 DC 的 CD103(+)亚群产生，并在实验性结肠炎期间下调。DC 产生的 TSLP 通过降低其产生白细胞介素（IL）-17 的能力并促进 Foxp3(+)T 细胞的发育，直接作用于 T 细胞。一致地，TSLP 通过直接作用于 T 细胞来保护免受结肠炎的发展，因为从 TSLPR(-/-)到 SCID 小鼠的幼稚 T 细胞的过继转移导致更严重的结肠炎，IL-17 产生 T 细胞和炎症细胞因子的频率增加。因此，我们描述了 TSLP 在肠道中的一种新的抗炎作用。
