PDF(Pubmed)
Abstract：
Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS).
We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease.
We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non-cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis.
These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin-gut interaction provides new insights into the coincidence of psoriasis and IBD.
We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease.
We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non-cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis.
These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin-gut interaction provides new insights into the coincidence of psoriasis and IBD.
摘要：
银屑病和炎症性肠病（IBD）都是发生在皮肤和肠道的慢性炎症性疾病，分别。众所周知，牛皮癣和IBD有很高的一致率，在这两种情况下，免疫细胞和微生物组组成发生了类似的变化。为了研究这种联系，我们使用了银屑病性皮炎和结肠炎的组合小鼠模型,其中小鼠用Toll样受体7激动剂咪喹莫特(IMQ)局部治疗,并饲喂葡聚糖硫酸钠(DSS).
我们将IMQ局部应用于B6小鼠（IMQ小鼠），随后在其饮用水中喂养2％DSS。疾病活动和免疫细胞表型进行了分析，使用16S核糖体RNA测序研究粪便样品的微生物组成。我们将IMQ小鼠的粪便移植到无菌IQI/Jic（IQI）小鼠中，并喂养DSS以评估肠道微生物群对疾病的影响。
我们首先证实IMQ小鼠表现出加速的DSS结肠炎。IMQ小鼠的肠道中IgD+和IgM+B细胞数量减少，非细胞因子产生性巨噬细胞数量增加。此外，IMQ小鼠的肠道微生物群受到干扰，约氏乳杆菌和罗伊氏乳杆菌种群显著减少。用IMQ小鼠粪便移植的无菌小鼠，但没有未经治疗的老鼠的粪便，还发展为严重的DSS结肠炎。
这些结果表明，皮肤炎症可能通过免疫和微生物学变化导致肠道的致病状况。我们发现了一种新的潜在的皮肤-肠道相互作用，为牛皮癣和IBD的巧合提供了新的见解。
我们将IMQ局部应用于B6小鼠（IMQ小鼠），随后在其饮用水中喂养2％DSS。疾病活动和免疫细胞表型进行了分析，使用16S核糖体RNA测序研究粪便样品的微生物组成。我们将IMQ小鼠的粪便移植到无菌IQI/Jic（IQI）小鼠中，并喂养DSS以评估肠道微生物群对疾病的影响。
我们首先证实IMQ小鼠表现出加速的DSS结肠炎。IMQ小鼠的肠道中IgD+和IgM+B细胞数量减少，非细胞因子产生性巨噬细胞数量增加。此外，IMQ小鼠的肠道微生物群受到干扰，约氏乳杆菌和罗伊氏乳杆菌种群显著减少。用IMQ小鼠粪便移植的无菌小鼠，但没有未经治疗的老鼠的粪便，还发展为严重的DSS结肠炎。
这些结果表明，皮肤炎症可能通过免疫和微生物学变化导致肠道的致病状况。我们发现了一种新的潜在的皮肤-肠道相互作用，为牛皮癣和IBD的巧合提供了新的见解。
