Abstract：
Psoriasis has long been associated with inflammatory bowel disease (IBD); however, a causal link is yet to be established. Here, we demonstrate that imiquimod-induced psoriasis (IMQ-pso) in mice disrupts gut homeostasis, characterized by increased proportions of colonic CX3CR1hi macrophages, altered cytokine production, and bacterial dysbiosis. Gut microbiota from these mice produce higher levels of succinate, which induce de novo proliferation of CX3CR1hi macrophages ex vivo, while disrupted gut homeostasis primes IMQ-pso mice for more severe colitis with dextran sulfate sodium (DSS) challenge. These results demonstrate that changes in the gut environment in psoriasis lead to greater susceptibility to IBD in mice, suggesting a two-hit requirement, that is, psoriasis-induced altered gut homeostasis and a secondary environmental challenge. This may explain the increased prevalence of IBD in patients with psoriasis.
摘要：
长期以来，牛皮癣与炎症性肠病（IBD）有关；然而，因果关系尚未建立。这里,我们证明咪喹莫特诱导的银屑病（IMQ-pso）在小鼠中破坏肠道稳态，以结肠CX3CR1hi巨噬细胞比例增加为特征，细胞因子产生改变，和细菌菌群失调。这些小鼠的肠道微生物群产生更高水平的琥珀酸，体外诱导CX3CR1hi巨噬细胞的从头增殖，而肠道稳态中断启动IMQ-pso小鼠更严重的结肠炎与葡聚糖硫酸钠（DSS）的攻击。这些结果表明，牛皮癣肠道环境的变化导致小鼠对IBD的易感性更高，建议两次命中的要求，也就是说,牛皮癣引起的肠道稳态改变和继发性环境挑战。这可以解释银屑病患者IBD患病率增加的原因。
