Kummola Laura, Ortutay Zsuzsanna, Chen Xi, Caucheteux Stephane, Hämäläinen Sanna, Aittomäki Saara, Yagi Ryoji, Zhu Jinfang, Pesu Marko, Paul William E, Junttila Ilkka S
Faculty of Medicine and Life Sciences, University of Tampere, 33520 Tampere, Finland.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 2017 May 15;198(10):3909-3918. doi: 10.4049/jimmunol.1600753. Epub 2017 Apr 12.
Thymic stromal lymphopoietin (TSLP) and IL-7 are related cytokines that mediate growth and differentiation events in the immune system. They signal through IL-7Rα-containing receptors. Target cells of TSLP in Th2 responses include CD4 T cells and dendritic cells (DCs). Although it has been reported that expression of TSLP receptor (TSLPR) on CD4 T cells is required for OVA-induced lung inflammation, DCs have also been shown to be target cells of TSLP. In this study, we show that murine ex vivo splenic DCs are unresponsive to TSLP, as they fail to phosphorylate STAT5, but in vitro overnight culture, especially in presence of IL-4, renders DCs responsive to both TSLP and IL-7. This induced responsiveness is accompanied by dramatic upregulation of IL-7Rα on DCs with little change in expression of TSLPR or of γ In splenic DCs, the induction of IL-7Rα occurs mainly in CD8 DCs. In vivo, we found that IL-4 has a differential regulatory role on expression of IL-7Rα depending on the cell type; IL-4 decreases IL-7Rα expression on CD4 T cells whereas it upregulates the expression on DCs. Our results indicate that the induction of IL-7Rα expression on DCs is critical for TSLP responsiveness and that IL-4 can upregulate IL-7Rα on DCs.
胸腺基质淋巴细胞生成素（TSLP）和白细胞介素-7（IL-7）是相关的细胞因子，它们介导免疫系统中的生长和分化事件。它们通过含IL-7Rα的受体发出信号。TSLP在Th2反应中的靶细胞包括CD4 T细胞和树突状细胞（DC）。尽管有报道称OVA诱导的肺部炎症需要CD4 T细胞上表达TSLP受体（TSLPR），但DC也已被证明是TSLP的靶细胞。在本研究中，我们发现小鼠离体脾DC对TSLP无反应，因为它们无法使信号转导子和转录激活子5（STAT5）磷酸化，但体外过夜培养，尤其是在IL-4存在的情况下，可使DC对TSLP和IL-7均产生反应。这种诱导的反应性伴随着DC上IL-7Rα的显著上调，而TSLPR或γ的表达变化不大。在脾DC中，IL-7Rα的诱导主要发生在CD8 DC中。在体内，我们发现IL-4对IL-7Rα的表达具有取决于细胞类型的差异调节作用；IL-4降低CD4 T细胞上的IL-7Rα表达，而它上调DC上的表达。我们的结果表明，DC上IL-7Rα表达的诱导对于TSLP反应性至关重要，并且IL-4可以上调DC上的IL-7Rα。
