近日,，來(lái)自山東省醫(yī)學(xué)科學(xué)院基礎(chǔ)醫(yī)學(xué)研究所的邵倩倩等人發(fā)現(xiàn)，金屬蛋白酶組織抑制因子3通過(guò)調(diào)節(jié)樹(shù)突細(xì)胞,，影響了Th1/Th2的平衡,。相關(guān)研究成果發(fā)表于5月17日發(fā)表在Blood上。
Th1,、Th2細(xì)胞是Th前體細(xì)胞 (pTh )在特定抗原刺激及多種因素綜合作用下,，發(fā)生功能性極化的結(jié)果。越來(lái)越多的證據(jù)表明,，Th1/Th2極化是免疫應(yīng)答調(diào)節(jié)中的關(guān)鍵環(huán)節(jié),。已有的研究表明,，細(xì)胞因子、抗原,、抗原遞呈細(xì)胞(APC ),、共刺激信號(hào)及一些基因調(diào)控因子均為T(mén)h1/Th2極化提供了重要信號(hào)。
金屬蛋白酶組織抑制因子3(TIMP-3)是能夠抑制基質(zhì)金屬蛋白酶的蛋白家族中的一種,，已經(jīng)發(fā)現(xiàn)它能夠作為一種炎癥檢查的介質(zhì),。
總所周知，炎癥引起了免疫反應(yīng)的激活,，然而,，TIMP-3是否也作用于免疫系統(tǒng)目前還不明確。在該研究中,，研究人員發(fā)現(xiàn)了TIMP-3新的功能：通過(guò)影響抗原呈遞細(xì)胞,，影響了Th1/Th2的極化。
首先,，在人樹(shù)突細(xì)胞通過(guò)p38MAPK通路發(fā)生分化的時(shí)候,，TIMP-3被發(fā)現(xiàn)通過(guò)IL-4而顯著上調(diào)。其次,，共刺激分子CD86的表達(dá)能夠被TIMP-3所抑制,。而且，在樹(shù)突細(xì)胞中,，IL-12的誘導(dǎo)以PI3K依賴的方式被顯著的抑制,。
此外，在TIMP-3存在下,，樹(shù)突細(xì)胞的成熟能夠刺激同種異體初始T輔助(Th)細(xì)胞表現(xiàn)出顯著的Th2極化,。重要的是，在自體免疫疾病原發(fā)免疫性血小板減少癥患者的血液樣品里,，研究發(fā)現(xiàn)TIMP-3與IL-4及血小板數(shù)目表現(xiàn)出正相關(guān)關(guān)系,，但是與IFN-γ卻表現(xiàn)出一個(gè)負(fù)相關(guān)關(guān)系。
總的來(lái)說(shuō),，該研究闡明了人體內(nèi)TIMP-3對(duì)Th1/Th2極化的新功能,。（生物谷Deepblue編譯）
doi: 10.1182/blood-2011-08-376418
PMC:
PMID:
Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells
Qianqian Shao*, Hao Ning*, Jiaju Lv*, Yanguo Liu, Xin Zhao, Guangwen Ren, Alei Feng, Qi Xie, Jintang Sun, Bingfeng Song, Yongmei Yang, Wenjuan Gao, Kejia Ding, Meixiang Yang, Ming Hou, Jun Peng, and Xun Qu
Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation.Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system.In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway.Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner.Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder–primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.
