Nakamizo Satoshi, Honda Tetsuya, Sato Tomohito, Al Mamun Md, Chow Zachary, Duan Kaibo, Lum Josephine, Tan Kahbing Jasmine, Tomari Kaori, Sato Reiko, Kitoh Akihiko, Tay Angeline S L, Common John E A, Guan Ng Lai, Setou Mitsutoshi, Ginhoux Florent, Kabashima Kenji
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.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Dermatology, School of Medicine, Hamamatsu University, Hamamatsu, Shizuoka, Japan.
J Allergy Clin Immunol. 2021 Aug;148(2):473-485.e10. doi: 10.1016/j.jaci.2021.02.032. Epub 2021 Mar 10.
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.
嗜中性粒细胞性毛囊炎是一种毛囊的炎症性疾病。在一些嗜中性粒细胞性毛囊炎中，如痤疮和化脓性汗腺炎患者，也观察到毛囊角化过度。嗜中性粒细胞性毛囊炎常由高脂饮食（HFD）诱发和/或加重。然而，HFD影响嗜中性粒细胞性毛囊炎的分子机制尚未完全明确。
我们的目的是阐明HFD如何促进嗜中性粒细胞性毛囊炎的发展。
给小鼠喂食HFD，并对其皮肤进行组织学、RNA测序和成像质谱分析。为了研究HFD对毛囊周围中性粒细胞聚集的影响，使用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）作为皮肤刺激物。
组织学分析显示，喂食HFD的小鼠皮肤出现毛囊角化过度。RNA测序分析表明，与角质化相关的基因，尤其是在上部毛囊角质形成细胞中，在喂食HFD的小鼠中显著上调。将PMA应用于皮肤可在喂食HFD的小鼠中诱发嗜中性粒细胞性毛囊炎，但在喂食正常饮食的小鼠中则不会。皮肤和毛囊周围中性粒细胞的聚集依赖于CXCR2信号传导，而CXCL1（一种CXCR2配体）主要由毛囊角质形成细胞产生。成像质谱分析显示，喂食HFD的小鼠皮肤中脂肪酸增加。将这些脂肪酸应用于皮肤可诱发毛囊角化过度，并导致即使在喂食正常饮食的小鼠中也出现PMA诱导的嗜中性粒细胞性毛囊炎。
HFD可通过诱导毛囊角化过度和增加毛囊周围中性粒细胞浸润，经由CXCR2信号传导促进嗜中性粒细胞性毛囊炎的发展。
