Immunity
Volume 50, Issue 1, 15 January 2019, Pages 121-136.e5
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Article
Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta

https://doi.org/10.1016/j.immuni.2018.11.003 Get rights and content
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Highlights

  • Neonatal skin is enriched with immature fat and adipogenic dermal fibroblasts

  • Dermal immature fat and adipogenic-antimicrobial dFBs are lost with age

  • TGF-β pathway promotes the age-related adipogenic-to-fibrotic switch of dFBs

  • Inhibition of TGFBR restores antimicrobial function of dFBs in adult mice

Summary

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.

Keywords

innate immunity
dermal white adipose tissue
dermal fibroblasts
adipocyte progenitors
adipocytes
Staphylococcus aureus
infection
cathelicidin
antimicrobial peptides
transforming growth factor beta

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