Interleukin-22 is a master regulator protecting and repairing tissues upon injury. It is a unique cytokine in that it is released from immune cells but does not target immune cells. Instead, it selectively targets epithelial cells resulting in an epithelial restricted biology. Upon an injury to the epithelium, e.g. caused by infection, inflammation, a chemical or physical insult, IL-22 is released from resident immune cells and induces epithelial tissue repair. It maintains the integrity of the tissue by preventing necrosis, stimulating cell proliferation and progenitor cell activation, controlling inflammation and securing anti-microbial defense. It is thus a “Survive and Recover” signal to the epithelium. The IL-22 activities can be distilled down to four main effects, which favorably tips the balance, during epithelial injury, to minimize tissue/organ damage and secure recovery:
ABOUT EPITHELIAL INJURY
The epithelium defines the barrier between the organism and its surroundings, whether in the form of a discrete epithelial barrier in tissues directly exposed to the environment (skin, lung, and intestine) or in epithelial derived organs (e.g. liver and kidney). Injury to the epithelium is a corner stone in the pathology of several serious human diseases, such as Inflammatory Bowel Disease (IBD) and late-stage liver disease. There is a large unmet medical need for treatments addressing epithelial injury.
The cause of injury can come from inflammation, a pathogenic insult (bacterial, viral or fungal), or a physical insult (e.g., wounds or surgery). The injury leads to tissue damage and inflammation which is often associated with regeneration deficiencies. Cytoki Pharma’s lead program features an engineered IL-22 protein that works selectively on epithelia and in an orchestrated fashion minimizes tissue damage, stimulates repair, and secures infection control through innate immunity (e.g., stimulation of anti-microbial peptides).
Inflammatory Bowel Disease (IBD) and IL-22
IBD comprises diseases characterized by chronic intestinal inflammation and tissue damage, with Ulcerative Colitis and Crohn’s Disease being the principal types of IBD. The prevalence is highest in the western world where up to 0.5 – 1% of the population is affected by the disease. IBD is currently treated medically with immunosuppressive or immunomodulatory treatments, or surgical intervention if not sufficiently controlled. Damage to the intestinal (epithelial) barrier is central to the disease pathology and repair of barrier dysfunction represents the largest unmet medical need in IBD. Intestinal barrier damage is believed to be the primary pathology preceding inflammation. IL-22 has been demonstrated to be key for maintaining and regenerating intestinal barrier integrity. Thus, long-acting IL-22 directly addresses the central pathology of IBD and represents a novel and differentiated treatment paradigm.
Late-Stage liver disease and IL-22
Late-stage liver disease such as cirrhosis and Acute on Chronic Liver Disease represents a growing health care problem and is associated with high morbidity, mortality, and a large unmet medical need. Long-acting IL-22 has great potential in these diseases as it addresses the key pathologies in an orchestrated fashion:
– Liver damage control through e.g. upregulation of anti-oxidative proteins
– Liver regeneration (restore function)
– Metabolic control (e.g. liver insulin sensitivity)
– Prevention of intestinal leakage (“leaky gut” fuels systemic inflammation and risk of infection)
IL-22 is secreted in response to tissue damage, infection or inflammation.