High-fat diet induces a predisposition to follicular hyperkeratosis and neutrophilic folliculitis in mice.


Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
08 2021
Historique:
received: 02 10 2020
revised: 23 02 2021
accepted: 26 02 2021
pubmed: 14 3 2021
medline: 21 10 2021
entrez: 13 3 2021
Statut: ppublish

Résumé

Neutrophilic folliculitis is an inflammatory condition of hair follicles. In some neutrophilic folliculitis, such as in patients with acne and hidradenitis suppurativa, follicular hyperkeratosis is also observed. Neutrophilic folliculitis is often induced and/or exacerbated by a high-fat diet (HFD). However, the molecular mechanisms by which an HFD affects neutrophilic folliculitis are not fully understood. Our aim was to elucidate how an HFD promotes the development of neutrophilic folliculitis. Mice were fed an HFD, and their skin was subjected to histologic, RNA sequencing, and imaging mass spectrometry analyses. To examine the effect of an HFD on neutrophil accumulation around the hair follicles, phorbol 12-myristate 13-acetate (PMA) was used as an irritant to the skin. Histologic analysis revealed follicular hyperkeratosis in the skin of HFD-fed mice. RNA sequencing analysis showed that genes related to keratinization, especially in upper hair follicular keratinocytes, were significantly upregulated in HFD-fed mice. Application of PMA to the skin induced neutrophilic folliculitis in HFD-fed mice but not in mice fed a normal diet. Accumulation of neutrophils in the skin and around hair follicles was dependent on CXCR2 signaling, and CXCL1 (a CXCR2 ligand) was produced mainly by hair follicular keratinocytes. Imaging mass spectrometry analysis revealed an increase in fatty acids in the skin of HFD-fed mice. Application of these fatty acids to the skin induced follicular hyperkeratosis and caused PMA-induced neutrophilic folliculitis even in mice fed a normal diet. An HFD can facilitate the development of neutrophilic folliculitis with the induction of hyperkeratosis of hair follicles and increased neutrophil infiltration around the hair follicles via CXCR2 signaling.

Sections du résumé

BACKGROUND
Neutrophilic folliculitis is an inflammatory condition of hair follicles. In some neutrophilic folliculitis, such as in patients with acne and hidradenitis suppurativa, follicular hyperkeratosis is also observed. Neutrophilic folliculitis is often induced and/or exacerbated by a high-fat diet (HFD). However, the molecular mechanisms by which an HFD affects neutrophilic folliculitis are not fully understood.
OBJECTIVE
Our aim was to elucidate how an HFD promotes the development of neutrophilic folliculitis.
METHODS
Mice were fed an HFD, and their skin was subjected to histologic, RNA sequencing, and imaging mass spectrometry analyses. To examine the effect of an HFD on neutrophil accumulation around the hair follicles, phorbol 12-myristate 13-acetate (PMA) was used as an irritant to the skin.
RESULTS
Histologic analysis revealed follicular hyperkeratosis in the skin of HFD-fed mice. RNA sequencing analysis showed that genes related to keratinization, especially in upper hair follicular keratinocytes, were significantly upregulated in HFD-fed mice. Application of PMA to the skin induced neutrophilic folliculitis in HFD-fed mice but not in mice fed a normal diet. Accumulation of neutrophils in the skin and around hair follicles was dependent on CXCR2 signaling, and CXCL1 (a CXCR2 ligand) was produced mainly by hair follicular keratinocytes. Imaging mass spectrometry analysis revealed an increase in fatty acids in the skin of HFD-fed mice. Application of these fatty acids to the skin induced follicular hyperkeratosis and caused PMA-induced neutrophilic folliculitis even in mice fed a normal diet.
CONCLUSION
An HFD can facilitate the development of neutrophilic folliculitis with the induction of hyperkeratosis of hair follicles and increased neutrophil infiltration around the hair follicles via CXCR2 signaling.

Identifiants

pubmed: 33713763
pii: S0091-6749(21)00363-8
doi: 10.1016/j.jaci.2021.02.032
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

473-485.e10

Informations de copyright

Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

Satoshi Nakamizo (S)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore; Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore; Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Tetsuya Honda (T)

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Dermatology, School of Medicine, Hamamatsu University, Hamamatsu, Shizuoka, Japan. Electronic address: hontetsu@kuhp.kyoto-u.ac.afn.

Tomohito Sato (T)

Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Md Al Mamun (M)

Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Zachary Chow (Z)

Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore.

Kaibo Duan (K)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.

Josephine Lum (J)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.

Kahbing Jasmine Tan (KJ)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore; Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore.

Kaori Tomari (K)

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Reiko Sato (R)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore; Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Akihiko Kitoh (A)

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Angeline S L Tay (ASL)

Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore.

John E A Common (JEA)

Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore.

Ng Lai Guan (NL)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.

Mitsutoshi Setou (M)

Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Florent Ginhoux (F)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore; Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore. Electronic address: Florent_Ginhoux@immunol.a-star.edu.sg.

Kenji Kabashima (K)

Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore; Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore; Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: kaba@kuhp.kyoto-u.ac.jp.

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