called gene PSMC6 It may be involved in driving inflammation and infiltration of immune cells into the primary infected glands Sjogren’s syndrome (pss), a study found.
PSMC6which was more expressed, or active, in the blood of PSS patients than in the blood of healthy people, and has also been linked to fewer T regulatory cells (Tregs), which normally dampen the activity of immune cells.
In a mouse model of Sjögren’s, silencing this gene reduced inflammation and immune cell infiltration, as well as increased the number of Tregs.
Collectively, PSMC6 can induce immune cell infiltration and inflammatory responses to promote virulence [primary Sjögren’s syndrome]providing us with a potential therapeutic target for the treatment of PSS.”
studying, “PSMC6 induces immune cell infiltration and the inflammatory response to primary exacerbations of Sjogren’s syndrome“in Journal of Human Genetics.
PSS is characterized by infiltration of immune cells into the saliva and tear glands
Infiltration of a variety of immune cells into the body’s moisture-producing glands—including the salivary, lacrimal, or tear-producing glands—is an essential feature of PSS. In this form of Sjögren’s disease, there are no other related diseases.
However, the mechanisms that drive immune cell infiltration in Sjogren’s disease are not fully understood. According to the researchers, a better understanding of these mechanisms could provide insight into new treatment approaches.
To this end, a team of scientists in China sought to better understand which genes might influence the migration of immune cells in the autoimmune disease. They screened genetic information from PSS patients that had been put into the Gene Expression Omnibus database.
Specifically, these datasets looked at messenger RNA (mRNA) levels in patients’ blood samples. mRNA is an intermediate molecule that forms when information stored in DNA is used to produce a protein. Thus, it can be used as a surrogate indicator of gene expression, or activity levels.
One data set contained samples from 30 PSS patients and 30 healthy individuals. Analysis of these samples revealed a total of 51 genes that were found to be at different levels between the two groups.
This difference indicates that these genes may be “key targets” in Sjögren’s disease, according to the researchers.
Another type of analysis identified a group of 334 genes that may be associated with pSS.
The two analyzes had 20 genes in common. Among them, most of them were involved in the regulation of immunity.
The top 10 genes were Sjögren-related RSL24D1, HAT1, PSMC6, COMMD8, POLR2K, MRPS28, CHMP5, BCL2A1, RPL22L1And LY96. All of these were expressed at high levels in the pSS samples.
Additional analyzes estimated the proportion of immune cell subsets that differed between PSS patients and healthy subjects. Specifically, patients appear to have higher percentages of memory B cells, some types of T cells, and activated dendritic cells. On the contrary, they had a lower incidence of Tregs than healthy individuals.
Tregs are a type of immune cell that regulate the activity of other immune cell types, and help dampen excessive immune and inflammatory responses.
In another dataset of 351 PSS patients, PSMC6 – one of the key genes previously found elevated in Sjögren – was negatively associated with Tregs, meaning that the higher the expression of PSMC6, Decreased abundance of Tregs.
“We speculate that PSMC6 may be involved in immune cell infiltration in pSS, and may negatively regulate the number and activity of Tregs,” the researchers write.
To dig deeper, the team turned to a mouse model of pSS. They found that the animals had significant immune cell infiltration and inflammation in the lacrimal and salivary glands, in addition to increased expression of PSMC6 In both glands and blood.
when PSMC6 Experimentally suppressed, immune cell infiltration and inflammation were reduced. The number of Tregs was increased, as were the levels of molecules key to Treg growth.
In short, this work explored the abnormal expression of PSMC6 during the pSS process,” the researchers wrote.
These results bring new insights into the role of PSMC6 in immune cell infiltration and inflammatory responses and to consider the possibility of treating pSS.”