miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.
miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.
复制标题
DOI：
10.1016/j.immuni.2014.09.015
复制
发表时间：
2014-10-16
期刊：
影响因子：
32.4
通讯作者：
O'Connell RM
中科院分区：
文献类型：
--
作者：
Hu R;Kagele DA;Huffaker TB;Runtsch MC;Alexander M;Liu J;Bake E;Su W;Williams MA;Rao DS;Möller T;Garden GA;Round JL;O'Connell RM
慢性炎症是大多数缩短人类寿命的疾病的一个促成因素。然而，维持慢性炎症反应的分子和细胞机制仍然知之甚少，这使得治疗这种有害疾病变得困难。使用由miR-146a缺乏引起的年龄依赖性炎症小鼠模型，我们证明miR-155有助于随着Mir146a - / -小鼠年龄的增长而出现的进行性炎症疾病。在分析炎症与健康中年小鼠的淋巴细胞后，我们发现T滤泡辅助细胞（Tfh）、生发中心（GC） B细胞和自身抗体的数量升高，所有这些都以mir -155依赖的方式发生。此外，生成了Cd4-cre Mir155fl/fl小鼠，并证明miR-155除了在B细胞中已确定的作用外，还在T细胞中具有促进多种情况下体液免疫的功能。综上所述，我们的研究发现，miR-146a和miR-155对Tfh细胞的发育进行反向调控，从而在慢性炎症期间驱动异常的GC反应。
Chronic inflammation is a contributing factor to most life shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a−/− mice grew older. Upon analyzing lymphocytes from inflamed versus healthy middle-aged mice we found elevated numbers of T follicular helper (Tfh) cells, germinal center (GC) B cells and autoantibodies, all occurring in a miR-155-dependent manner. Further, Cd4-cre Mir155fl/fl mice were generated and demonstrated that miR-155 functions in T cells, in addition to its established role in B cells, to promote humoral immunity in a variety of contexts. Taken together, our study discovers that miR-146a and miR-155 counter-regulate Tfh cell development that drives aberrant GC reactions during chronic inflammation.