Neutrophils Require SHP1 To Regulate IL-1β Production and Prevent Inflammatory Skin Disease
Neutrophils Require SHP1 To Regulate IL-1β Production and Prevent Inflammatory Skin Disease
复制标题
DOI：
10.4049/jimmunol.1002702
复制
发表时间：
2011-01-15
影响因子：
4.4
通讯作者：
Roberts, Andrew W.
中科院分区：
文献类型：
--
作者：
Croker, Ben A.;Lewis, Rowena S.;Roberts, Andrew W.
中性粒细胞募集、活化和处置的调节是局限性炎症的关键。SHP 1（Y208 N/Y208 N）突变小鼠发生IL-1 R依赖性的严重皮肤炎性疾病。嗜中性粒细胞数量的遗传减少和对感染的嗜中性粒细胞反应足以防止这种疾病的自发发生。来自SHP 1（Y208 N/Y208 N）小鼠的嗜中性粒细胞显示由于对MyD 88依赖性和MyD 88非依赖性信号的反应改变而增加的pro-IL-1 β产生。SHP 1（Y208 N/Y208 N）小鼠中的IL-1 R依赖性炎性疾病的发展独立于半胱天冬酶1和蛋白酶3以及中性粒细胞弹性蛋白酶。响应于Fas配体（IL-1 β产生的半胱天冬酶1非依赖性诱导剂），来自SHP 1（Y208 N/Y208 N）小鼠的中性粒细胞产生升高水平的IL-1 β，但显示降低的半胱天冬酶3和半胱天冬酶7活化。在缺乏SHP 1的中性粒细胞中，IL-1 β诱导高水平的pro-IL-1 β，表明存在旁分泌IL-1 β环。这些数据表明，SHP 1（Y208 N/Y208 N）小鼠中的嗜中性粒细胞和IL-1依赖性疾病是TLR和IL-1 R信号传导负调控丧失的结果。免疫学杂志，2011，186：1131-1139。
The regulation of neutrophil recruitment, activation, and disposal is pivotal for circumscribed inflammation. SHP1(Y208N/Y208N) mutant mice develop severe cutaneous inflammatory disease that is IL-1R dependent. Genetic reduction in neutrophil numbers and neutrophilic responses to infection is sufficient to prevent the spontaneous initiation of this disease. Neutrophils from SHP1(Y208N/Y208N) mice display increased pro-IL-1 beta production due to altered responses to MyD88-dependent and MyD88-independent signals. The IL-1R-dependent inflammatory disease in SHP1(Y208N/Y208N) mice develops independently of caspase 1 and proteinase 3 and neutrophil elastase. In response to Fas ligand, a caspase 1-independent inducer of IL-1 beta production, neutrophils from SHP1(Y208N/Y208N) mice produce elevated levels of IL-1 beta but display reduced caspase 3 and caspase 7 activation. In neutrophils deficient in SHP1, IL-1 beta induces high levels of pro-IL-1 beta suggesting the presence of a paracrine IL-1 beta loop. These data indicate that the neutrophil-and IL-1-dependent disease in SHP1(Y208N/Y208N) mice is a consequence of loss of negative regulation of TLR and IL-1R signaling. The Journal of Immunology, 2011, 186: 1131-1139.