New Therapeutic Strategy For Autoimmune Diseases

Therapeutic Strategy For Autoimmune Diseases

New Therapeutic Strategy For Autoimmune Diseases

Autoimmune diseases are often triggered by a T-cell imbalance in our system. Like forces ready for battle against an invading army, the T cells are pivotal players in defending the body against infection or injury. When under siege, the immune system quickly releases a burst of disease-fighting T-cells to engulf and defeat the invaders. Specialized blood cells—called “T effector cells”—are mobilized to fight the attack. Once the enemy is vanquished, regulatory T cells (Tregs) are supposed to quickly sweep away any T effector cells left on the battlefield.

Inflammatory diseases result when T effector cells linger in the bloodstream, circulating to distant organs and attacking the joints. The overgrowth of T effector cells contributes to the development of chronic inflammatory diseases such as rheumatoid arthritis (RA), a disabling disease that attacks and destroys cartilage and bone, leaving the joint painful and inflamed.

In his laboratory, Arthritis National Research Foundation funded researcher Kai Yang, PhD, is studying the cellular and molecular mechanisms of inflammatory diseases at St. Jude Children’s Research Hospital.

“My current research represents a new therapeutic strategy for autoimmune diseases,” he says. “We are investigating how Tregs may help to prevent arthritis and related diseases. Tregs are a specialized subset of CD4+ T cells with a central role in immune tolerance and prevention of autoimmunity.”

Autoimmune Diseases | Kai Yang

The interplay between immune regulatory mechanisms and T cell responses is crucial to the body’s defense system. When it goes wrong, it sparks a body-wide inflammatory response.

In autoimmune diseases, the body turns on itself as circulating T effector cells seek, attack, and destroy normal tissue. “Our goal is to understand the basic immune mechanisms involved in rheumatoid arthritis,” says Dr. Yang. “If we can enhance the capability of Tregs in suppressing T effector cells, we may be able to prevent this joint-damaging inflammatory response.”

In the hope of finding a better way to treat RA and other autoimmune diseases, Dr. Yang is also studying how pro-inflammatory T helper cells intended to safeguard the body’s immune system from disease-causing microbes also promote inflammation. The body’s protective cellular reaction turns toxic when thrown into overdrive by persistent assault by bacteria or pathogens. Scientists are studying how inflammation — marked by redness, heat, swelling and pain—sets the stage for RA and other autoimmune diseases.

Over the past decade, medications that modify the body’s “biologic response” have made breathtaking strides against inflammatory diseases by blocking chemical messengers in the immune system. Biologic therapies don’t simply reduce pain and swelling, but also block the pathways that trigger inflammation and destroy the joints.

Dr. Yang is focused on understanding the crucial role of a molecular pathway—called PTEN signaling — in the normal immune system. His research targets a complex web of signaling and metabolic pathways with the potential to influence the development of joint-damaging inflammation. “My recent study highlights the crucial role of PTEN signaling in the development of an autoimmune disease,” he explains.

What is the role of PTEN signaling in metabolic pathways that influence autoimmune diseases?

Rheumatoid Arthritis | Kai Yang

Dr. Yang is studying the complex interplay between molecular and metabolic pathways. Someday, scientists may be able to harness PTEN signaling to potentiate the function of Tregs — while also suppressing the T effector cells that promote inflammatory diseases.

“Understanding the underlying mechanisms of PTEN signaling in autoimmune diseases holds the promise to improve arthritis therapy,” says Dr. Yang. “The grant from the Arthritis National Research Foundation provides a unique opportunity to investigate novel therapeutic targets that will potentially benefit patients with rheumatoid arthritis.”

Article Author
Arthritis National Research Foundation

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

  • Avatar
    John Crance
    Posted at 08:25h, 08 December Reply

    So, I wonder … is the considered new therapy to be used to downregulate CD4/CD8 outright … or is it an upstream cytokine (IL-1, TNF-a, IL-6, Il-8, Il-18) inhibitor?

    • admin
      Posted at 10:13h, 23 December Reply

      From Dr. Yang, “Regulatory T cells (Tregs) are essential for maintaining immune tolerance and preventing autoimmunity. They restrain the responses of autoreactive effector T cells that promote the initiation and perpetuation of lupus in humans and mice. However, Treg cells are decreased and loss suppressive function in patients and mice with active lupus. My previous research highlighted that PTEN coordinates molecular and metabolic pathways to enhance stability and function of Treg cells. My current study aims to understand molecular and metabolic mechanisms that can rectify the functional defects of Treg cells in lupus.”

  • Avatar
    Tracie Carlson
    Posted at 20:10h, 11 December Reply

    I’m curious to know the answer to Johns question.

  • Avatar
    Posted at 18:22h, 24 December Reply

    Keep up the promising work. Thank you Dr. Yang and your team for your efforts. SLE is terrible. Been battling over 6yrs. Thankful for everyday with my children, family and life. Keeping my hopes and plans lively…May God gives us a remedy to normal T Cell balance and etc. through dedicated researchers, physicians, and nurses and his strengthening wisdom with grace everyday. SPC

  • Avatar
    Isabel Dijkstra
    Posted at 01:50h, 16 January Reply

    I have spondolytic arthritis. My CD4 count and CD4:CD8 ratio were above normal when last measured. Is this relevant?

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