Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23
Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23
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DOI：
10.1038/s41467-019-12540-8
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发表时间：
2019-10-04
影响因子：
16.6
通讯作者：
Furtado, Glaucia C.
中科院分区：
文献类型：
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作者：
Chen, Lili;Strohmeier, Valentina;Furtado, Glaucia C.
新生儿炎症性疾病与严重的发病率有关，但其潜在的炎症因子及其潜在的效应机制尚不清楚。在这里，我们表明，坏死性小肠结肠炎在新生小鼠是伴随着升高的IL-23和IL-22和减少生产的胰腺酶。这些表型反映在新生小鼠CX 3CR 1（+）骨髓细胞或角质形成细胞中过表达IL-23。小鼠不能生长并过早死亡，表现出全身性炎症、营养吸收不良以及介导碳水化合物、蛋白质和脂质的消化和吸收的肠和胰腺基因的表达降低。无菌环境得到改善，IL-22的基因消除恢复了过表达IL-23的小鼠的正常生长。从机制上讲，IL-22直接作用于胰腺腺泡细胞水平，以降低胰腺相关转录因子Ia（PTF 1a）的表达。这些结果表明，生命早期IL-23和IL-22的产生增加对胰腺酶分泌和食物吸收具有负面影响。
Neonatal inflammatory diseases are associated with severe morbidity, but the inflammatory factors underlying them and their potential effector mechanisms are poorly defined. Here we show that necrotizing enterocolitis in neonate mice is accompanied by elevation of IL-23 and IL-22 and decreased production of pancreatic enzymes. These phenotypes are mirrored in neonate mice overexpressing IL-23 in CX3CR1(+) myeloid cells or in keratinocytes. The mice fail to grow and die prematurely, displaying systemic inflammation, nutrient malabsorption and decreased expression of intestinal and pancreatic genes mediating digestion and absorption of carbohydrates, proteins, and lipids. Germ-free environment improves, and genetic ablation of IL-22 restores normal growth in mice overexpressing IL-23. Mechanistically, IL-22 acts directly at the level of pancreatic acinar cells to decrease expression of the pancreas associated transcription factor la (PTF1a). These results show that augmented production of IL-23 and IL-22 in early life has a negative impact on pancreatic enzyme secretion and food absorption.