Igniting the rheumatoid arthritis flame through a cellular cascade

May 30, 2018

Osaka - Chronic inflammatory disorders, including autoimmune diseases such as rheumatoid arthritis, involve the action of various inflammatory molecules (cytokines) produced by cells of the immune system. One such cytokine, IL-17, is produced by Th17 cells, which are white blood cells that provide host defense against pathogens, as well as mediating inflammatory reactions. Although Th17 cells are lead players in autoimmune disease, the way in which they control other inflammatory cells had been unclear.

Now, an international team of researchers led by Osaka University has used a mouse model of rheumatoid arthritis to investigate how Th17 cells interact with other cells at the site of inflammation and influence cytokine production. They reported their findings in the journal Immunity.

Several inflammatory cytokines, including IL-6 and TNFα, cause joint inflammation in rheumatoid arthritis. The disease progresses through the interaction of T cells of the immune system with specialized cells in the joint lining (synovium), which promotes the destruction of bone and cartilage. The recent development of new anti-rheumatic drugs such as TNF and IL-6 inhibitors has dramatically improved the quality of life of many patients with rheumatoid arthritis, but treatment for 30% of these patients remains a challenge. Therefore, novel therapies are eagerly awaited.

The inflammatory cytokine GM-CSF activates cells involved in innate and adaptive immune systems, which represent non-specific defense mechanisms and specific learned responses to foreign substances, respectively. GM-CSF particularly triggers scavenger white blood cells (macrophages) and immune cell messengers known as dendritic cells.

The team found that GM-CSF was crucial for the development of arthritis in the mouse model. "GM-CSF produced both by stromal cells of the connective tissue and T cells contributed to joint inflammation in the mice, but only stromal cell-derived GM-CSF was needed to initiate arthritis," study first author Keiji Hirota explains. "We also showed that stromal cells secreted GM-CSF in response to stimulation by IL-17 from inflammatory Th17 cells."

GM-CSF was also found to be secreted by a group of innate immune cells, which expanded in number within inflamed joints in response to IL-17 production by Th17 cells and other inflammatory cytokines. This contributed to the maintenance and development of rheumatoid arthritis in the mice.

"Our findings outline an inflammatory network controlled by autoimmune Th17 cells and involving stromal cells and innate immune cells, which leads to the onset and development of autoimmune arthritis," corresponding author Shimon Sakaguchi says. "By selectively removing GM-CSF-producing cells from the mouse synovium, we significantly reduced the severity of arthritis. This suggests the usefulness of developing such a novel immunotherapeutic approach that targets the cellular network to reduce chronic joint inflammation."
-end-
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.

Website: http://resou.osaka-u.ac.jp/en/top

Osaka University

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.