Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología, Buenos Aires, Argentina.
CONICET - Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Buenos Aires, Argentina.
Eur J Immunol. 2019 Nov;49(11):2095-2102. doi: 10.1002/eji.201848024. Epub 2019 Jul 31.
There is increasing evidence of the relevant connection and regulation between the gut and skin immune axis. In fact, oral administration of lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) prevents the development of UV-induced skin tumors in chronically exposed mice. Here we aim to evaluate whether this LTA is able to revert UV-induced immunosuppression as a mechanism involved in its anti-tumor effect and whether it has an immunotherapeutic effect against cutaneous squamous cell carcinoma. Using a mouse model of contact hypersensitivity, we demonstrate that LTA overcomes UV-induced skin immunosuppression. This effect was in part achieved by modulating the phenotype of lymph node resident dendritic cells (DC) and the homing of skin migratory DC. Importantly, oral LTA reduced significantly the growth of established skin tumors once UV radiation was discontinued, demonstrating that it has a therapeutic, besides the already demonstrated preventive antitumor effect. The data presented here strongly indicates that oral administration of LTA represents a promising immunotherapeutic approach for different conditions in which the skin immune system is compromised.
越来越多的证据表明肠道和皮肤免疫轴之间存在相关联系和调节。事实上,口服鼠李糖乳杆菌 GG(LGG)来源的脂磷壁酸(LTA)可预防慢性暴露于紫外线的小鼠发生 UV 诱导的皮肤肿瘤。在这里,我们旨在评估这种 LTA 是否能够逆转 UV 诱导的免疫抑制,作为其抗肿瘤作用的一种机制,以及它是否对皮肤鳞状细胞癌具有免疫治疗作用。使用接触超敏反应的小鼠模型,我们证明 LTA 可克服 UV 诱导的皮肤免疫抑制。这种作用部分是通过调节淋巴结驻留树突状细胞(DC)的表型和皮肤迁移性 DC 的归巢来实现的。重要的是,一旦停止 UV 辐射,口服 LTA 可显著减少已建立的皮肤肿瘤的生长,这表明它具有治疗作用,除了已经证明的预防抗肿瘤作用。这里呈现的数据强烈表明,口服 LTA 代表了一种有前途的免疫治疗方法,可用于皮肤免疫系统受损的多种情况。