Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton's tyrosine kinase-dependent pathway
Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton's tyrosine kinase-dependent pathway
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DOI：
10.1038/s41563-018-0271-6
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发表时间：
2019-03-01
期刊：
影响因子：
41.2
通讯作者：
Gause, William C.
中科院分区：
文献类型：
--
作者：
Mishra, Pankaj K.;Palma, Mark;Gause, William C.
对微粒子暴露可产生的先天无菌炎症反应的启动知之甚少。在这里，我们报告了一种有效的2型免疫反应，与中性粒细胞、嗜酸性粒细胞和交替激活的(M2)巨噬细胞的聚集有关，对大小相似的无菌微粒的反应与假体相关的磨损碎片有关。虽然白细胞介素33(IL-33)和2型细胞因子的升高独立于caspase-1炎症信号，但这种反应依赖于Bruton‘s酪氨酸激酶(BTK)。IL-33是由巨噬细胞产生的，巨噬细胞对IL-33的依赖表达足以启动2型反应。对患者假体周围组织的炎症分析也显示了接受翻修手术的患者在无菌条件下的2型反应。这些发现表明，微粒诱导的无菌炎症是由激活的巨噬细胞产生IL-33启动的。他们进一步表明，BTK和IL-33都可能为磨屑引起的假体周围炎症提供治疗靶点。
Initiation of the innate sterile inflammatory response that can develop in response to microparticle exposure is little understood. Here, we report that a potent type 2 immune response associated with the accumulation of neutrophils, eosinophils and alternatively activated (M2) macrophages was observed in response to sterile microparticles similar in size to wear debris associated with prosthetic implants. Although elevations in interleukin-33 (IL-33) and type 2 cytokines occurred independently of caspase-1 inflammasome signalling, the response was dependent on Bruton's tyrosine kinase (BTK). IL-33 was produced by macrophages and BTK-dependent expression of IL-33 by macrophages was sufficient to initiate the type 2 response. Analysis of inflammation in patient periprosthetic tissue also revealed type 2 responses under aseptic conditions in patients undergoing revision surgery. These findings indicate that microparticle-induced sterile inflammation is initiated by macrophages activated to produce IL-33. They further suggest that both BTK and IL-33 may provide therapeutic targets for wear debris-induced periprosthetic inflammation.