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*步是要證實在感染MCMV的小鼠中,NK細胞的確產(chǎn)生IL-10。研究人員注意到,在高度感染的小鼠中,NK細胞在被感染約3.5天后產(chǎn)生IL-10,3.5天過后,他們會產(chǎn)生IFN-γ,這種蛋白質有助于增強免疫應答,而不是化解。
在實驗室培養(yǎng)中,他們發(fā)現(xiàn),只有那些約3.5天后感染的細胞會產(chǎn)生IL-10。隨后的實驗表明,本質上,暴露于病毒是沒有必要的,而是幾輪復制和增殖(約3天)能夠產(chǎn)生IL-10。
“總而言之,這些研究表明,無論是在體外條件下獨立的感染下,還是在體內感染過程中,N??K??細胞的廣泛增殖與IL-10產(chǎn)生有關,”作者說。
已經(jīng)表明,IL-10的產(chǎn)生是與NK細胞的增殖有關,Tarrio,比隆和同事尋求更多的證據(jù):觸發(fā)開關產(chǎn)生IL-10的NK細胞的機制。
他們在感染的小鼠中,對NK細胞增殖前和后的全基因組的構象進行比較。他們發(fā)現(xiàn),NK細胞尚未發(fā)生增殖過程時,IL-10基因被緊緊地包裹起來,而無法進行表達。細胞進行增殖時的IL-10基因被打開使其更容易表達。
“當我們得到這些結果時,大家都非常興奮,因為在體內的感染過程中,從一個細胞群中挖掘表觀遺傳改變是相當不俗的,” Tarrio說。
The first step was to confirm that NK cells did produce IL-10 in mice infected with MCMV. The researchers noted that NK cells produce IL-10 after about 3.5 days of infection in highly infected mice, and after 3.5 days, they produce IFN-γ, a protein that helps boost the immune response rather than defuse .
In laboratory culture, they found that only those cells infected about 3.5 days later produced IL-10. Subsequent experiments showed that, essentially, exposure to the virus is not necessary, but several rounds of replication and proliferation (about 3 days) are capable of producing IL-10.
"All in all, these studies show that the extensive proliferation of N? K cells is associated with IL-10 production both independently of in vitro conditions and during in vivo infection," the authors said.
It has been shown that the production of IL-10 is related to the proliferation of NK cells, and Tarrio Billund and colleagues seek more evidence of the mechanism that triggers the switch to produce IL-10-producing NK cells.
They compared the genome-wide conformation of NK cells before and after their proliferation in infected mice. They found that when NK cells have not yet proliferated, the IL-10 gene is tightly packed and can not be expressed. When the cells proliferate, the IL-10 gene is opened to make it easier to express.
"When we got these results, everyone was very excited, because in the body of the infection, mining epigenetic changes from a cell population is quite impressive," Tarrio said.