Non-canonical IL-22 receptor signaling remodels the mucosal barrier during fungal immunosurveillance.

Our bodies are home to trillions of microbes, many of which are harmless or even helpful. But when the balance is disrupted, some of these microbes—like the fungus Candida albicans—can cause infections, especially in vulnerable populations like newborns or people with weakened immune systems. This study reveals how our immune system responds to early fungal colonization by temporarily reshaping the lining of the mouth to prevent infection. This study found that when Candida begins to grow in the mouth, the immune system doesn’t just attack it—it actually remodels the mucosal barrier, the protective layer of cells lining the mouth, in both adult and newborn mice. This remodeling strengthens the barrier and helps prevent the fungus from invading deeper tissues. This process is driven by a molecule called interleukin-22 (IL-22), which activates a signaling pathway involving STAT3 and a unique receptor complex. Together, these signals prompt certain epithelial cells in the mouth to multiply and change, reinforcing the barrier against fungal invasion. Interestingly, this remodeling only happens in the mouth—not in other parts of the body—and it fades once the immune system has developed a more targeted response to the fungus. This study offers valuable insight into how the body naturally regenerates and strengthens its own tissues in response to microbial threats. Understanding these mechanisms could help develop new therapies that mimic or enhance the body’s own regenerative responses—especially in patients with compromised immune systems or damaged mucosal barriers. Learning how the immune system and epithelial cells work together to protect the body, allows for the design of more targeted regenerative therapies.