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Immunity. 2019 Jan 15;50(1):121-136.e5. doi: 10.1016/j.immuni.2018.11.003. Epub 2018 Dec 26.

Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta.

Author information

1
School of Pharmaceutical Sciences, Xiamen University, Xiamen, China; Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: lingjuan.zhang@xmu.edu.cn.
2
Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
4
Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
5
Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing 210042, China.
6
Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: rgallo@ucsd.edu.

Abstract

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:

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

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