Organs are not only spectators, but also active participants in fighting autoimmune diseases

A study published today in the Wall Street Journal by researchers at the University of Pittsburgh School of Medicine suggests that organs affected by autoimmune diseases can fight back by "depleting" immune cells, which use methods similar to cancer cell evasion tests to cause damage. Clinical investigation.

These findings are based on a mouse model of systemic lupus erythematosus (SLE), called lupus, that explains why autoimmune diseases may take a long time to cause significant organ damage. They can also explain the harmful autoimmune side effects of widely used cancer immunotherapy drugs on normal organs.

Mark Shlomchik, senior author, said: "These findings do change our current understanding of autoimmune tissue damage and suggest that if we can develop targeted ways to enhance the body's natural ability to regulate the immune system, we can treat these diseases more effectively." Doctor of Medicine, Doctor of Medicine, and UPMC conferred upon Professor and Chairman of the Department of Immunology of Peter Medical School and an investigator at the UPMC Immune Transplantation and Treatment Center.

In autoimmune diseases such as lupus, immune cells usually protect against invaders, such as bacteria or cancer cells, rather than starting to recognize that their cells are foreign and attack them. In lupus nephritis, a kidney disease associated with SLE, a large number of autoreactive cells, known as renal infiltrating T cells (KITs), are thought to be activated, causing damage over time.

To find out how these cells actually cause kidney damage, Dr. Jeremy Tilstra, an assistant professor of medicine at Pitt Medical School, and researchers at the Shlomchik Laboratory began studying these cells in three different lupus nephritis mouse models.

As the researchers expected, there were millions of KITs in the kidneys, but surprisingly, they were not as active as previously thought.

Tilstra said, "T cells are there, but they are not very active. In fact, the opposite is true." They are lazy, ineffective killers, and are not well separated. This is totally unexpected.

Experiments show that these KIT cells do not respond to stimuli as normal T cells do - they neither release characteristic inflammatory proteins nor reproduce well. These cells also consume much less energy, showing signs of metabolic failure.

Interestingly, the exhausted kit is very similar to the T cells found inside the tumor. Affected kidney cells are also similar to tumor cells in some ways because they express higher levels of a protein called PD-L1, which cancer cells use to inhibit entry into tumor T cells.

"Our results suggest that the body can actively fight autoimmune diseases, rather than sit back and ignore them. The similarity between lupus and T cells in the kidney and tumor is of great importance, "Shlomchik noted. This suggests that the ability to suppress T cells is not an abnormal mechanism by which cancer cells develop in some way to defeat the immune system, but rather an existing natural mechanism by which tumors have adopted autoimmune diseases.

In the future, researchers plan to extend the study to patients with lupus to see if they can find similar failing T cells in urine or tissue samples.