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      IL-23 protein structures

      What is IL-23?

      This pro-inflammatory protein is the target of potential Johnson & Johnson medications that could help treat autoimmune conditions such as psoriasis, inflammatory bowel disease and rheumatoid arthritis.

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      The interleukin 23 receptor, or IL-23 (shown above), has a big job to do. When your body is under attack from threats such as bacteria or fungi, IL-23—a cytokine, or protein, embedded in the body—activates your immune system to protect against illness.

      Some people, however, produce too much IL-23. And while that might sound like an even more beneficial response, it’s actually just the opposite. Too much IL-23 increases inflammation and raises the risk for certain autoimmune conditions.

      “IL-23 controls immune cells,” explains Daniel Cua, Ph.D., Distinguished Fellow, Immunology, Johnson & Johnson Innovative Medicine. For instance, if you cut yourself, immune cells gather to fight off pathogens that might cause an infection. “But your body can overproduce IL-23 even if there’s no infection,” says Dr. Cua, who is often called the “father” of the IL-23 pathway, thanks to his involvement in the discovery of IL-23 and its role in inflammatory disease more than two decades ago.

      If you can block IL-23, you can target the disease process, and that turns off many downstream effects, promoting tissue healing and reducing activities.
      Daniel Cua, Ph.D.
      Distinguished Fellow, Immunology, at Johnson & Johnson Innovative Medicine

      An overabundance of IL-23 can open the door for inflammation, especially of the skin, joints and gut, he says. And that can lead to chronic autoimmune conditions, including psoriasis, psoriatic arthritis, ulcerative colitis and Crohn’s disease. Johnson & Johnson has been at the forefront of developing treatments targeting IL-23 so that patients can achieve durable, symptom-free remission and improve their quality of life.

      How IL-23 causes autoimmune diseases

      Scientists aren’t exactly sure why some people overproduce IL-23. Dr. Cua says it’s likely related to genetic factors and the body’s response to previous contact with pathogens: It needed to create more IL-23 to heal itself and basically went too far. In those instances, “the immune system continues to make IL-23, even though the infection is gone,” he adds. “It causes a lot of additional inflammatory reactions that drive the disease process.”

      Take, for instance, inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease. “Pathogens in the gut can turn on the IL-23 pathway to fight the infection, but then the body struggles to turn off IL-23, leading to a continually overactive immune system,” says Dr. Cua. That triggers cells in the lining of the intestine and colon to continue to “multiply inappropriately,” he explains, and produce inflammatory factors, causing IBD.

      Prolonged IBD-related inflammation can damage the gastrointestinal (GI) tract. Patients deal with persistent diarrhea, rectal bleeding, abdominal pain and fatigue; some end up needing surgery to remove parts of the GI tract.

      Targeting IL-23 improves patients’ lives

      Blocking IL-23 is the best way to suppress IBD and certain other autoimmune diseases, Dr. Cua says. Johnson & Johnson has been working on developing medications that do just that.

      “If you can block IL-23, you can target the disease process, and that turns off many downstream effects,” promoting tissue healing and reducing disease activities, he explains. “It’s remarkably effective.”

      Johnson & Johnson’s research and development has made great strides in developing treatments that target IL-23. Initially, treatments focused on P40 inhibition, which reduced autoimmune inflammation by blocking IL-23 and another cytokine called interleukin 12 (IL-12). Further research led to specific IL-23 blocking and more effective inhibition of autoimmune inflammation.

      Scientists at Johnson & Johnson have also been developing oral investigational treatments that block the IL-23 receptor. Dr. Cua says the company is currently evaluating the safety and effectiveness of these investigational treatments in patients with moderate to severe psoriatic disease and IBD.

      Having the option to take a pill to treat their autoimmune conditions would be potentially game-changing for patients, says Dr. Cua. “We will continue discovering, developing and delivering transformational treatments with patient need grounding every step of our work. At the end of the day, our mission is remission—for all patients living with immune-mediated diseases.”

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