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Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta
Immunity ( IF 19.734 ) Pub Date : 2018-12-26 , DOI: 10.1016/j.immuni.2018.11.003
Ling-juan Zhang, Stella Xiang Chen, Christian F. Guerrero-Juarez, Fengwu Li, Yun Tong, Yuqiong Liang, Marc Liggins, Xu Chen, Hao Chen, Min Li, Tissa Hata, Ye Zheng, Maksim V. Plikus, Richard L. Gallo

Dermal fibroblasts (dFBs) resist infection by locally differentiating into adipocytes and producing cathelicidin antimicrobial peptide in response toStaphylococcus 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 toS. aureusinfection. These results provide insight into changes that occur in the skin innate immune system between the perinatal and adult periods of life.
更新日期:2018-12-28

 

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