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阻断p38 MAPK的升高可改善老年人的免疫反应
作者:小柯机器人 发布时间:2020/4/10 10:28:58

英国伦敦大学Derek W. Gilroy小组在研究中取得进展。他们发现阻止p38丝裂原激活的蛋白激酶(MAPK)升高可以帮助老年人恢复红细胞增长和炎症消退。相关论文于2020年4月6日在线发表在《自然-免疫学》杂志上

使用人类皮肤急性炎症模型,研究人员发现尽管年轻人和老年人之间有相似的炎症发生阶段,但是老年人的炎症分型性阶段受到了严重损害。这是由T细胞免疫球蛋白粘蛋白受体4(TIM-4)减少引起的,TIM-4是表达在巨噬细胞上的磷脂酰丝氨酸受体,能够吞噬凋亡小体,即所谓的胞吞作用。老年个体TIM-4的减少是由巨噬细胞p38 MAPK活性升高造成的。

老年个体口服活性p38抑制剂可挽救TIM-4的表达、清除凋亡小体并恢复巨噬细胞分型。因此,抑制老年人的p38可以恢复其分型活力,使该阶段与年轻人更为相似。这是人类中鉴定的第一个分型缺陷并可以被成功逆转,从而凸显了将靶向分型生物学作为治疗慢性炎症造成疾病的潜能。

研究人员表示,年龄的增加会改变先天免疫介导的反应;但是,尚不完全清楚人类发生这些变化的基础机制。

附:英文原文

Title: Blocking elevated p38 MAPK restores efferocytosis and inflammatory resolution in the elderly

Author: Roel P. H. De Maeyer, Rachel C. van de Merwe, Rikah Louie, OliviaV. Bracken, Oliver P. Devine, Daniel R. Goldstein, Mohib Uddin, Arne N. Akbar, Derek W. Gilroy

Issue&Volume: 2020-04-06

Abstract: Increasing age alters innate immune–mediated responses; however, the mechanisms underpinning these changes in humans are not fully understood. Using a human dermal model of acute inflammation, we found that, although inflammatory onset is similar between young and elderly individuals, the resolution phase was substantially impaired in elderly individuals. This arose from a reduction in T cell immunoglobulin mucin receptor-4 (TIM-4), a phosphatidylserine receptor expressed on macrophages that enables the engulfment of apoptotic bodies, so-called efferocytosis. Reduced TIM-4 in elderly individuals was caused by an elevation in macrophage p38 mitogen-activated protein kinase (MAPK) activity. Administering an orally active p38 inhibitor to elderly individuals rescued TIM-4 expression, cleared apoptotic bodies and restored a macrophage resolution phenotype. Thus, inhibiting p38 in elderly individuals rejuvenated their resolution response to be more similar to that of younger people. This is the first resolution defect identified in humans that has been successfully reversed, thereby highlighting the tractability of targeting pro-resolution biology to treat diseases driven by chronic inflammation.

DOI: 10.1038/s41590-020-0646-0

Source: https://www.nature.com/articles/s41590-020-0646-0

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex