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Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta.
Immunity ( IF 25.5 ) Pub Date : 2018-12-26 , DOI: 10.1016/j.immuni.2018.11.003 Ling-Juan Zhang 1 , Stella Xiang Chen 2 , Christian F Guerrero-Juarez 3 , Fengwu Li 2 , Yun Tong 2 , Yuqiong Liang 4 , Marc Liggins 2 , Xu Chen 5 , Hao Chen 5 , Min Li 5 , Tissa Hata 2 , Ye Zheng 4 , Maksim V Plikus 3 , Richard L Gallo 2
Immunity ( IF 25.5 ) Pub Date : 2018-12-26 , DOI: 10.1016/j.immuni.2018.11.003 Ling-Juan Zhang 1 , Stella Xiang Chen 2 , Christian F Guerrero-Juarez 3 , Fengwu Li 2 , Yun Tong 2 , Yuqiong Liang 4 , Marc Liggins 2 , Xu Chen 5 , Hao Chen 5 , Min Li 5 , Tissa Hata 2 , Ye Zheng 4 , Maksim V Plikus 3 , Richard L Gallo 2
Affiliation
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Dermal fibroblasts (dFBs) resist infection by locally differentiating into adipocytes and producing cathelicidin antimicrobial peptide in response to Staphylococcus aureus (S. aureus). Here, we show that neonatal skin was enriched with adipogenic dFBs and immature dermal fat that highly expressed cathelicidin. The pool of adipogenic and antimicrobial dFBs declined after birth, leading to an age-dependent loss of dermal fat and a decrease in adipogenesis and cathelidicin production in response to infection. Transforming growth factor beta (TGF-β), which acted on uncommitted embryonic and adult dFBs and inhibited their adipogenic and antimicrobial function, was identified as a key upstream regulator of this process. Furthermore, inhibition of the TGF-β receptor restored the adipogenic and antimicrobial function of dFBs in culture and increased resistance of adult mice to S. aureus infection. These results provide insight into changes that occur in the skin innate immune system between the perinatal and adult periods of life.
中文翻译：
与年龄相关的皮肤脂肪先天免疫抗菌功能丧失是由转化生长因子 Beta 介导的。
真皮成纤维细胞 (dFB) 通过局部分化为脂肪细胞并产生对金黄色葡萄球菌 (S. aureus) 作出反应的导管素抗菌肽来抵抗感染。在这里，我们展示了新生儿皮肤富含脂肪形成的 dFB 和高表达导管素的未成熟真皮脂肪。脂肪生成和抗菌 dFB 的池在出生后下降，导致皮肤脂肪的年龄依赖性损失以及响应感染的脂肪生成和导管素的产生减少。转化生长因子 β (TGF-β) 作用于未定型的胚胎和成人 dFB，并抑制其脂肪形成和抗菌功能，被确定为该过程的关键上游调节剂。此外，抑制 TGF-β 受体可恢复培养中 dFBs 的脂肪形成和抗菌功能，并增加成年小鼠对金黄色葡萄球菌感染的抵抗力。这些结果有助于深入了解围产期和成年期皮肤先天免疫系统发生的变化。
更新日期：2018-12-26
中文翻译：
与年龄相关的皮肤脂肪先天免疫抗菌功能丧失是由转化生长因子 Beta 介导的。
真皮成纤维细胞 (dFB) 通过局部分化为脂肪细胞并产生对金黄色葡萄球菌 (S. aureus) 作出反应的导管素抗菌肽来抵抗感染。在这里，我们展示了新生儿皮肤富含脂肪形成的 dFB 和高表达导管素的未成熟真皮脂肪。脂肪生成和抗菌 dFB 的池在出生后下降，导致皮肤脂肪的年龄依赖性损失以及响应感染的脂肪生成和导管素的产生减少。转化生长因子 β (TGF-β) 作用于未定型的胚胎和成人 dFB，并抑制其脂肪形成和抗菌功能，被确定为该过程的关键上游调节剂。此外，抑制 TGF-β 受体可恢复培养中 dFBs 的脂肪形成和抗菌功能，并增加成年小鼠对金黄色葡萄球菌感染的抵抗力。这些结果有助于深入了解围产期和成年期皮肤先天免疫系统发生的变化。
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