PSMC6 Gene May Cause Inflammation in Primary Sjögren’s Syndrome: Study | Gene also related to the infiltration of immune cells into the glands

A gene called PSMC6 may be involved in driving inflammation and immune cell infiltration into affected glands by primary Sjogren’s syndrome (pSS), one study found.

PSMC6which was more expressed or activated in the blood of pSS patients than in healthy people, was also linked to lower numbers of regulatory T cells (Tregs), which normally work to dampen immune cell activity.

In a Sjögren’s mouse model, silencing this gene led to decreased inflammation and immune cell infiltration, as well as an increase in the number of Tregs.

Collectively, PSMC6 could induce immune cell infiltration and inflammatory responses to promote the onset of [primary Sjögren’s syndrome]providing us with a potential therapeutic target to treat pSS,” the researchers wrote.

The study, “PSMC6 induces immune cell infiltration and inflammatory response to aggravate primary Sjögren’s syndrome”, was published in the journal of human genetics.

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An illustration of a DNA strand showing its ribbon-like structure.

pSS labeled by immune cell infiltration into saliva and lacrimal glands

Infiltration of a variety of immune cells into the body’s moisture-producing glands, including the salivary and lacrimal, or tear-producing, glands is a key feature of SpS. In this form of Sjögren’s, there are no other related diseases.

However, the mechanisms driving immune cell infiltration in Sjögren’s disease are not fully understood. According to the researchers, a better understanding of these mechanisms could offer information on new treatment approaches.

To that end, a team of scientists in China aimed to better understand which genes might influence immune cell migration in autoimmune disease. They examined the genetic information of pSS patients found in the omnibus gene expression database.

Specifically, these data sets looked at messenger RNA (mRNA) levels in the patients’ blood samples. mRNA is an intermediate molecule that forms when the information stored in DNA is used to make a protein. Therefore, it can be used as a surrogate indicator of a gene’s expression or activity levels.

One data set contained samples from 30 pSS patients and 30 healthy individuals. An analysis of these samples revealed a total of 51 genes that were found at different levels between the two groups.

That difference suggests that these genes may be “key targets” in Sjögren’s, according to the researchers.

Another type of analysis identified a group of 334 genes that could be associated with pSS.

The two analyzes had 20 genes in common. Of these, most were involved in immune regulation.

The top 10 Sjögren-related genes were RSL24D1, HAT1, PSMC6, COMMD8, POLR2K, MRPS28, CHMP5, BCL2A1, RPL22L1Y LY96. All were expressed at high levels in pSS samples.

Additional analyzes estimated that the proportion of various immune cell subsets differed between pSS patients and healthy people. Specifically, the patients appeared to have higher proportions of memory B cells, some types of T cells, and activated dendritic cells. On the contrary, they had a lower proportion of Tregs compared to healthy individuals.

Treg cells are a type of immune cell that work to regulate the activity of other types of immune cells and help dampen excessive immune and inflammatory responses.

In another data set including 351 pSS patients, PSMC6 – one of the key genes previously found to be elevated in Sjögren’s disease – was negatively correlated with Tregs, meaning that the higher the expression of PSMC6, the lower the abundance of Tregs.

“We speculate that PSMC6 may be involved in immune cell infiltration into pSS and may downregulate the number and activity of Tregs,” the researchers wrote.

To dig further, 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, as well as increased expression of PSMC6 in both glands and in the blood.

When PSMC6 was experimentally silenced, immune cell infiltration and inflammation were reduced. The number of Tregs increased, as did the levels of key molecules for Treg growth.

“In summary, this work uncovered the abnormal expression of PSMC6 during the pSS process,” the researchers wrote.

“These results provide new insights into the role of PSMC6 in immune cell infiltration and inflammatory responses and further consider its potential for pSS therapy,” they concluded.

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