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巨噬細(xì)胞功能新發(fā)現(xiàn)：分化關(guān)鍵蛋白Trib1
點(diǎn)擊次數(shù)：2981 發(fā)布時(shí)間：2013-4-9
巨噬細(xì)胞至少有兩個(gè)亞類(lèi),，即M1型和M2型,。人類(lèi)全基因組關(guān)聯(lián)研究表明TRIB1參與脂質(zhì)代謝。現(xiàn)在大阪大學(xué)WPI免疫前沿研究中心等處的研究人員發(fā)現(xiàn)TRIB1通過(guò)控制M2類(lèi)巨噬細(xì)胞的分化,，在脂肪組織維持和脂質(zhì)代謝紊亂上發(fā)揮關(guān)鍵作用,。
巨噬細(xì)胞至少有兩個(gè)亞類(lèi)，即M1型和M2型,。M1型巨噬細(xì)胞參與促炎反應(yīng),，且在宿主防御細(xì)菌和病毒感染中發(fā)揮核心作用。M2巨噬細(xì)胞與抗炎反應(yīng),、寄生蟲(chóng)感染,、組織重構(gòu)、纖維化以及腫瘤疾病發(fā)展相關(guān),。 Trib1是個(gè)銜接蛋白,，與泛素連接酶COP1相互作用參與蛋白降解。人類(lèi)全基因組關(guān)聯(lián)研究表明TRIB1參與脂質(zhì)代謝,。
現(xiàn)在,，大阪大學(xué)WPI免疫前沿研究中心等處的研究人員，發(fā)現(xiàn)Trib1對(duì)F4/80 + MR +組織內(nèi)在巨噬細(xì)胞的分化至關(guān)重要,，且這些巨噬細(xì)胞和M2巨噬細(xì)胞,、酸性粒細(xì)胞具有共同的特性（稱(chēng)之為M2類(lèi)巨噬細(xì)胞）。但是,，Trib1在M1髓系細(xì)胞就不會(huì)發(fā)揮這種作用,。相關(guān)研究論文于2013年3月20日發(fā)表在Nature雜志上。
Trib1缺陷導(dǎo)致各種器官中M2類(lèi)巨噬細(xì)胞急劇減少,，如骨髓,、脾臟、肺以及脂肪組織,。在Trib1缺失的骨髓細(xì)胞中,，C / EBP α的異常表達(dá)要為巨噬細(xì)胞分化缺陷負(fù)責(zé),。沒(méi)有想到的是，造血細(xì)胞缺乏 Trib1的小鼠,，減少了脂肪組織塊,，并伴隨著脂肪分解增加，即使是在正常飲食條件下,。
M2類(lèi)巨噬細(xì)胞的補(bǔ)充可緩解這種病理學(xué)現(xiàn)象,。這表明，這類(lèi)巨噬細(xì)胞的缺乏是引發(fā)脂肪分解的原因,。為了應(yīng)對(duì)高脂肪飲食,，造血細(xì)胞缺乏 Trib1的小鼠發(fā)育中會(huì)呈現(xiàn)高甘油三酯血癥、胰島素抗性,，同時(shí)增加促炎細(xì)胞基因誘導(dǎo),。
總之，這些結(jié)果表明Trib1在脂肪組織維持和脂質(zhì)代謝紊亂上發(fā)揮關(guān)鍵作用,，而其作用是通過(guò)控制組織內(nèi)在M2類(lèi)巨噬細(xì)胞的分化實(shí)現(xiàn)的,。
原文摘要：
Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages
Macrophages consist of at least two subgroups, M1 and M2 （refs 1, 2, 3）. Whereas M1 macrophages are proinflammatory and have a central role in host defence against bacterial and viral infections4, 5, M2 macrophages are associated with responses to anti-inflammatory reactions, helminth infection, tissue remodelling, fibrosis and tumour progression6. Trib1 is an adaptor protein involved in protein degradation by interacting with COP1 ubiquitin ligase7. Genome-wide association studies in humans have implicated TRIB1 in lipid metabolism8, 9, 10. Here we show that Trib1 is critical for the differentiation of F4/80+MR+ tissue-resident macrophages—that share characteristics with M2 macrophages （which we term M2-like macrophages）—and eosinophils but not for the differentiation of M1 myeloid cells. Trib1 deficiency results in a severe reduction of M2-like macrophages in various organs, including bone marrow, spleen, lung and adipose tissues. Aberrant expression of C/EBPα in Trib1-deficient bone marrow cells is responsible for the defects in macrophage differentiation. Unexpectedly, mice lacking Trib1 in haematopoietic cells show diminished adipose tissue mass accompanied by evidence of increased lipolysis, even when fed a normal diet. Supplementation of M2-like macrophages rescues the pathophysiology, indicating that a lack of these macrophages is the cause of lipolysis. In response to a high-fat diet, mice lacking Trib1 in haematopoietic cells develop hypertriglyceridaemia and insulin resistance, together with increased proinflammatory cytokine gene induction. Collectively, these results demonstrate that Trib1 is critical for adipose tissue maintenance and suppression of metabolic disorders by controlling the differentiation of tissue-resident M2-like macrophages.