Nav: Home

Advancing our understanding of how the disease lupus is prevented in healthy individuals

October 30, 2016

A group of researchers at Tokyo Medical and Dental University(TMDU) have identified a molecule that stops the immune system from mistakenly reacting to a component of the body's own cells, which could improve our ability to treat systemic lupus erythematosus (SLE), a disease associated with inflammation of various organs including kidney, brain, skin, heart and lung.

Tokyo, Japan - Systemic lupus erythematosus (SLE) is a disease that affects various organs including kidney, brain, skin, heart and lung, due to immune cells mistakenly attacking molecular complexes within it. Although there are treatments that can ameliorate the symptoms, there is no cure. People with lupus suffer increased risks of infection and metabolic diseases due to treatments. In a major breakthrough in the fight against this disease, researchers at TMDU and their colleagues have studied a molecule expressed on immune cells that prevents these cells from reacting with the body and causing SLE, and explained the mechanism behind its action, raising hopes for new treatments of this disease.

The immune system features cells that can recognize potentially damaging agents, such as toxins, cancerous cells, and bacteria and viruses. Upon encountering such agents, immune cells act to neutralize and remove them; these actions include labeling them as dangerous, engulfing and destroying them, or releasing proteins called antibodies that can specifically identify the same agents elsewhere in the body. However, this recognition can sometimes go awry, leading the immune system to attack healthy cells or tissues, which can have devastating results. Such conditions are known as autoimmune diseases, which include lupus, a disease in which various organs are damaged by inflammation.

Previous studies have suggested some cells and molecules that could be involved in this condition, but definitive proof has not been obtained and the exact mechanism by which SLE develops, or by which it is prevented from developing in healthy individuals, has not been determined. Building on this previous work, a team including researchers at TMDU has shown that a molecule called CD72 prevents a certain type of immune cell from mistakenly reacting with a protein complex within the body. The team confirmed this by analyzing immune responses in cells in which CD72 had been removed, and by comparing the ability of different variants of CD72 to prevent SLE.

"When we knocked out CD72 in mouse B cells, they were specifically stimulated by the self-antigen Sm/RNP and released antibodies against this antigen," says Takeshi Tsubata of the Department of Immunology at TMDU. "The lack of CD72 meant that another receptor on B cells could bind to Sm/RNP, which activated the B cells and led to the symptoms of SLE."

To confirm these findings, the team analyzed different variants of CD72, one of which was suggested to be defective. They found that these variants differed in their potency of preventing development of SLE. They also used X-ray crystallography to show the exact mechanisms of compromised binding of these variants to Sm/RNP.

"We now know that CD72 prevents immune responses which lead to SLE without affecting responses to microbes and cancer cells," Takeshi Tsubata of TMDU says. "If we can develop a method to augments capability of CD72, this will treat patients with SLE without unwanted effects."
-end-
The article "CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous Toll-like receptor 7 ligand Sm/RNP" was published in The Journal of Experimental Medicine at doi: 10.1084/jem.20160560.

Tokyo Medical and Dental University

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".