Topical antibiotics limit depigmentation in a mouse model of vitiligo

IF 3.9 3区 医学 Q2 CELL BIOLOGY
Ahmed Ahmed Touni, Rachel Sohn, Cormac Cosgrove, Rohan S. Shivde, Emilia R. Dellacecca, Rasha T. A. Abdel-Aziz, Kettil Cedercreutz, Stefan J. Green, Hossam Abdel-Wahab, I. Caroline Le Poole
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Abstract

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.

Abstract Image

Abstract Image

局部抗生素可限制白癜风小鼠模型的脱色。
口服新霉素会影响小鼠的肠道微生物群并延缓白癜风的发展,而局部使用抗生素同样可以使微生物群保持皮肤健康并延缓脱色。在这里,我们研究了对易患白癜风的 pmel-1 小鼠进行 6 周局部抗生素治疗的效果。将杆菌肽、新孢子菌素或凡士林涂抹在一只脱色小鼠的侧腹上,同时用凡士林处理所有小鼠的对侧侧腹。每周对腹侧色素沉着进行量化。我们发现,局部新孢子菌素治疗可显著减少色素沉着,并在治疗区域外显示出效果,而百雀羚软膏则没有效果。在治疗过程中,从每组四只具有代表性的小鼠身上采集的粪便样本显示,新孢子菌治疗与肠道中Alistipes属丰度的降低相一致,而皮肤微生物组在终点时的相关变化则不太明显。任何一种抗生素治疗都会导致MR1表达减少,从而可能限制粘膜相关不变T细胞的活化,而新孢子菌素处理过的皮肤则选择性地显示CD8+ T细胞丰度显著降低。后一项发现与多种炎症标志物表达减少和调节性 T 细胞密度明显增加相一致。我们对良好皮肤和口服抗生素治疗的研究都使用了新霉素化合物,在这两种情况下,粪便样本中的微生物变化都最为明显。综上所述,应用含新霉素的抗生素可以介导皮肤Treg浸润,从而限制白癜风的发展。我们的研究强调了短期应用抗生素限制脱色性白癜风的治疗潜力。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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