{"title":"使用 Janus 激酶抑制剂 oclacitinib 可分别下调和上调特应性皮炎患犬外周血 T 细胞中 CD25 和 Foxp3 的表达。","authors":"Agnieszka Jasiecka-Mikołajczyk, Piotr Socha","doi":"10.1186/s12917-024-04340-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Oclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4<sup>+</sup> and CD8<sup>+</sup> T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28.</p><p><strong>Results: </strong>The study showed that the mean percentage and absolute count of CD4<sup>+</sup> and CD8<sup>+</sup> T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4<sup>+</sup> T cells and the mean percentage and absolute count of CD8<sup>+</sup> T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25<sup>+</sup>CD4<sup>+</sup> and CD25<sup>+</sup>CD8<sup>+</sup> T cells were significantly decreased; the reduction in the percentage of CD25<sup>+</sup>CD4<sup>+</sup> T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3<sup>+</sup>CD4<sup>+</sup> T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils.</p><p><strong>Conclusions: </strong>The findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4<sup>+</sup> and CD8<sup>+</sup> T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4<sup>+</sup> Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4<sup>+</sup> regulatory T cells - resulting in the shift of the CD4<sup>+</sup> Treg cell (i.e. Foxp3<sup>+</sup>CD4<sup>+</sup>)/activated Teff (i.e. CD25<sup>+</sup>CD4<sup>+</sup>) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL.</p>","PeriodicalId":9041,"journal":{"name":"BMC Veterinary Research","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515184/pdf/","citationCount":"0","resultStr":"{\"title\":\"Treatment with oclacitinib, a Janus kinase inhibitor, down-regulates and up-regulates CD25 and Foxp3 expression, respectively, in peripheral blood T cells of dogs with atopic dermatitis.\",\"authors\":\"Agnieszka Jasiecka-Mikołajczyk, Piotr Socha\",\"doi\":\"10.1186/s12917-024-04340-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Oclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4<sup>+</sup> and CD8<sup>+</sup> T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28.</p><p><strong>Results: </strong>The study showed that the mean percentage and absolute count of CD4<sup>+</sup> and CD8<sup>+</sup> T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4<sup>+</sup> T cells and the mean percentage and absolute count of CD8<sup>+</sup> T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25<sup>+</sup>CD4<sup>+</sup> and CD25<sup>+</sup>CD8<sup>+</sup> T cells were significantly decreased; the reduction in the percentage of CD25<sup>+</sup>CD4<sup>+</sup> T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3<sup>+</sup>CD4<sup>+</sup> T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils.</p><p><strong>Conclusions: </strong>The findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4<sup>+</sup> and CD8<sup>+</sup> T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4<sup>+</sup> Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4<sup>+</sup> regulatory T cells - resulting in the shift of the CD4<sup>+</sup> Treg cell (i.e. Foxp3<sup>+</sup>CD4<sup>+</sup>)/activated Teff (i.e. CD25<sup>+</sup>CD4<sup>+</sup>) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL.</p>\",\"PeriodicalId\":9041,\"journal\":{\"name\":\"BMC Veterinary Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515184/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Veterinary Research\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1186/s12917-024-04340-0\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Veterinary Research","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1186/s12917-024-04340-0","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景:奥克替尼(Oclacitinib,OCL)是一种Janus激酶抑制剂,是一种新型免疫调节/免疫抑制剂,已被批准作为治疗犬特应性皮炎(AD)的一线药物。这项研究的目的是在临床条件下,即在患有特应性皮炎的狗体内,从安全性和治疗作用的免疫机制两方面研究 OCL 对 CD4+ 和 CD8+ T 细胞及其选定亚群的影响。八只狗按推荐剂量接受了28天的OCL治疗。分别在第 0、7、14 和 28 天采集血液样本:研究表明,在使用 OCL 治疗的第 14 天和第 28 天,CD4+ 和 CD8+ T 细胞的平均百分比和绝对计数与相应的基线值(即治疗前的数值)没有差异。在治疗的第 7 天,CD4+ T 细胞的平均绝对计数、CD8+ T 细胞的平均百分比和绝对计数均显著增加。研究发现,在治疗的第 14 天,CD25+CD4+ 和 CD25+CD8+ T 细胞的平均百分比和绝对数量明显减少;在治疗的第 28 天,CD25+CD4+ T 细胞百分比的减少持续存在。用 OCL 治疗两周后,Foxp3+CD4+ T 细胞的平均百分比有所增加,而且这种效应在最后一个时间点持续存在。使用 OCL 治疗可降低嗜酸性粒细胞水平,但不影响嗜碱性粒细胞、单核细胞和中性粒细胞的绝对计数:研究结果有力地表明结论:研究结果有力地表明:(a) 就 OCL 对 PB CD4+ 和 CD8+ T 细胞数量的影响而言,每月使用该药物治疗应被视为相对安全;(b) 减少嗜酸性粒细胞的作用和下调 CD4+Teff 细胞上调的 CD25 表达,可能是该药物治疗犬 AD 的作用机制的重要因素;(c) 诱导性 Foxp3 表达的 CD4+ 调节性 T 细胞的生成--导致 CD4+ Treg 细胞(即 Foxp3+CD4+ Treg 细胞)的转移--可能是该药物治疗犬 AD 的作用机制的重要因素。e. Foxp3+CD4+)/activated Teff(i.e. CD25+CD4+)细胞平衡,使 Treg 细胞比例增加--这可能被认为是 OCL 产生免疫调节/免疫抑制特性的另一种机制。
Treatment with oclacitinib, a Janus kinase inhibitor, down-regulates and up-regulates CD25 and Foxp3 expression, respectively, in peripheral blood T cells of dogs with atopic dermatitis.
Background: Oclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4+ and CD8+ T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28.
Results: The study showed that the mean percentage and absolute count of CD4+ and CD8+ T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4+ T cells and the mean percentage and absolute count of CD8+ T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25+CD4+ and CD25+CD8+ T cells were significantly decreased; the reduction in the percentage of CD25+CD4+ T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3+CD4+ T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils.
Conclusions: The findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4+ and CD8+ T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4+ Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4+ regulatory T cells - resulting in the shift of the CD4+ Treg cell (i.e. Foxp3+CD4+)/activated Teff (i.e. CD25+CD4+) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL.
期刊介绍:
BMC Veterinary Research is an open access, peer-reviewed journal that considers articles on all aspects of veterinary science and medicine, including the epidemiology, diagnosis, prevention and treatment of medical conditions of domestic, companion, farm and wild animals, as well as the biomedical processes that underlie their health.