| Autor: |
Mao-Jie Wang, Yong-Yue Xu, HarmJan Vos, Can Gulersonmez, Edwin Stigter, Johan Gerritsen, Marc Pages Gallego, Robert van Es, Li Li, Hao Deng, Ling Han, Run-Yue Huang, Chuan-Jian Lu, Boudewijn MT Burgering |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.01.21.477183 |
| Popis: |
Psoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Immune cell activation requires increased glucose consumption, consequently limiting glucose availability for other cell types like keratinocytes. In psoriasis Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes. Here we show that miR-31 expression in keratinocytes is induced by limited glucose availability and increases survival under limiting glucose conditions, by increasing glutamine metabolism. In addition, miR-31 induced glutamine metabolism results in secretion of specific metabolites (aspartate and glutamate) but also immuno-modulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibition of glutaminase (GLS) using CB-839 impedes miR31-induced metabolic rewiring and secretion of immuno-modulatory factors. Concordantly, pharmacological targeting of GLS alleviated psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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