Cao Xuetao's team revealed the interaction of host non-immune cells with inherent immune cells.

Intense and orderly preparation scenes, every day in the body's immune system staged in turn - the enemy touches the cordon; the alert patrol system sounds an emergency alarm; signal soldiers in place to send out the signal of organizing defensive counter-attacks; the base provides material support; the combat troops are fully deployed; after the installation, immediately, the enemy fire.
recently, "Cell" magazine published online the Chinese Academy of Engineering, Nankai University President Cao Xuetao team's important findings, explained the "base" and "combat troops" to cooperate with the life mechanism.
", "Just like a shell is loaded before the assembly leads, we find that when immune cells migrate out of blood vessels, they bind a particular molecule to the endothelial cells of the blood vessels, which in turn 'detonates' the immune cells' ability to kill bacteria." Cao Xuetao, author of the
" paper, explained that the body uses this mechanism to limit immune cells only after migration to the infected site to "justify" to avoid the immune system's "fire."
the highlight of the study is the revelation of the interaction of host non-immune cells with inherent immune cells to regulate the activation and maturation of immune cells.
" inflammation occurs, blood in the blood vessels decelerates from the state of the axial flow, immune cells roll forward on the endothelial of the blood vessels, and constantly come into contact with the endothelial blood vessels, which we first found to have biological significance. Dr. Xu Xiaoqing, the first author of the
" paper and a researcher at the Center for Immunotherapy at the Institute of Basic Medicine of the Chinese Academy of Medical Sciences, told Science daily.
a "role-playing table" to understand the macrophage "eat" bacterial line in order to better understand this complex cross-cell line, first clear the "role-playing table": the enemy, that is, intracellular infection bacteria, including Listeria, tuberculosis bacteria, etc.; It is found that the virus emits interferon alpha or beta, which is gamma, after receiving the signal of inflammatory factors, the base (host cell, this time angioplasty cell) will express a large number of endothelial cell selectors (E-selectin); "It's an eight-year study,"
.
" Xu Xiaoqing introduced, in which the study of molecular mechanisms takes the longest time, accounting for half of the total research time.
" we found that a mouse that knocked out the E-selectin gene and was infected with Listeria, the macrophages behaved differently from normal mice.
" Xu Xiaoqing said, active macrophages not only flow less out of the blood vessels, but also reduce their activity.
a normal-carrying e-selectin gene in mice inflamed by bacterial infection, blood flow slows down, macrophages roll into contact with the inner epidermis of the blood vessels, and spreads from the walls of blood vessels to reach the site where inflammation occurs, starting to kill bacteria.
but once the expression of E-selectin was lacking, the mice showed fewer troops arriving at the "battlefield" and less lethal.
"E-selectin missing mice after bacterial infection, macrophages should reach the spleen, causing the spleen to swell, but its spleen size did not change.
, another count of our results also showed a significant decline in the number of macrophages.
"Our tests on cell-active molecules also prove that macrophages are blocked from activating, " xu said.
"At the cellular level, E-selectin is an essential element for activating macrophages.
"s studies have only known that E-selectin can mediate immune cells to swim out of blood vessels to the inflammatory site to be antibacterial, but it is not known that in this process it also has the function of activated immune cells.
" Xu Xiaoqing said, the team wanted to demonstrate at the molecular level how activation works.
side of the high side of the low "seesaw" concentration prompts the path "blocking point" because the activation of macrophages, meaning that interferon stoopers reach the surface of macrophages and surface receptors binding, will trigger activation, so we just began to guess whether interferon radon is less, did not stimulate macrophage activation.
" Xu Xiaoqing recalled, but the test of interferon radon gave them a negative answer - the expression of interferon radon in the serum is not low, but abnormally high.
", "We feel very novel, the front end increases, the back end decreases, that should be the middle link there is a problem."
" Xu Xiaoqing said, the cell path is like a real-life pipeline, "intercepting" or "silting" points before and after there will be a clear contrast between the ocean and dry.
"seesaw"-style concentrations reveal that "silting" occurs in the inner pathways of macrophages.
what caused the silt? "When interferon sphonyls activate macrophages, there is a very specific pathway called the JAK-STAT pathway.
we found that the activity of this pathway decreased.
" Xu Xiaoqing said that biopsies of several key active molecules in this pathway confirmed speculation that the pathway's activity decreased.
the critical molecular activity along a road is not high, indicating that the siltation of this pathway occurs at the source, that is, the entire pathway is not activated from the beginning, rather than interrupted in the cell. "We suspect that there is a problem with the receptors of interferon in the cell membrane,"
.
," Xu Xiaoqing said.
there has been research to show that the receptors on the cell membrane are made up of two sub-cells, ifN-Sr1 and IFN-R2.
ifN-R1 composition is expressed on the surface of nuclear cells, mainly in combination with IFN-N-Sr.
IFN-R2 is easily located in the cell membrane and induced expression on the cell membrane surface to form a functional IFN-gamma receptor after the bacteria infect the host.
can be understood as, R1 raw and live on the cell membrane, the role is "outreach", the reception to visit the interferon, and R2 is later transferred to the membrane, the role is "internal pass", external signals can be transferred to the cell, induced intracellular reactions, to see R2 workers do not work.
the entire cross-cell line of the "checking" research work to be carried out here, can basically target - for The E-selectin missing mice, the problem is the macrophage surface interferon receptor, its R2 part did not enter the normal working state.
the internal exploration of the cell strict "exclusive" proof of the restoration of the truth to target, the task force took 4 years.
the next four years will be the most difficult mechanism research work, the location spent in search is also transferred to the cell, as well as if-the-r2 from birth to transfer process analysis.
the essence of R2 sub-base is protein, the team from its translation began to "find the bottom of the root."
data show that the protein is translated by ribosome, and the protein that needs to be translocation situated to the endosome, Gorky body to be modified before reaching the cell membrane.
"some proteins that reach the cell membrane may also be swallowed in the cell and then digested."
" Xu Xiaoqing said, all of these cells in the circulation in the mechanism of the study to prove and fumble, in order to finally "check out" an IFN-R2 lifeline, and prove that the process is affected by E-selectin.
", "We're going to explore which steps in this cycle were affected in the mice that were missing from E-selectin."
" Xu Xiaoqing said, studying each step requires a different approach.
, for example, the transcription of the coded IFN-R2 gene was not affected by E-selectin, and the team tested the relevant RNA and found no reduced effect.
"We detected the product of the R2 protein at different stages from translation to modification, and saw where the concentration decreased.
" Xu Xiaoqing said, and finally, by separating the Gorky body, it was found that the R2 sub-levels on the Gorky body increased dramatically, but less on the membrane.
"seesaw" concentration again, the target is locked, the crux of the problem is in the "seesaw" fulcrum.
" eventually found the problem in the Gorky body to the cell membrane at this point.
," Xu Xiaoqing said.
combined with the effects of the previous E-selectin molecule on the macrophage tyrosine kinase pathway, and found a common focus point, the team finally concluded that the E-selectin molecule influenced the selective phosphorylation of the tyrosine kinase molecule to R2, and the phosphorylation of R2 binds to the transport protein to promote its transport from gorkytosis to the cell membrane.
visible, without E-selectin, there would be no combination of R2 and transport protein, so it is difficult to film.
", "There are many possible paths inside the cell, and we'll all have to prove it one by one, and finally find out that path."
" Xu Xiaoqing said, which is why Cell magazine can receive, all the proofs should be strong.
team even eliminated other possible factors in the blood by performing bone marrow stem cell transplants on mice, proving that only E-selectin can produce this function.
analysis suggests that the study is the first to explain the expression of receptors on the cell membrane from a dynamic perspective, and for the first time confirms that in inflammatory environments, vascular endothelial cells can pre-activate macrophages that are about to perform important phagocytosis through E-Selectin.
Source: Science Daily.