Grant: Project Grant

Patients with severe skin diseases, such as chronic dermatitis and lymphedema, are vulnerable to skin and soft tissue infections (SSTI). The infection in them tends to spread rapidly and extensively within the affected skin, penetrate the soft tissues and connective tissues, and persist for months, posing a significant risk of life-threatening sepsis, causing a significant socioeconomic and healthcare burden. The goal of this project to investigate whether lymph node stromal cells (LNSCs) can be a novel target to improve host immunity in infection in skin diseases. The lymph node (LN) functions as a hub for generating immune protection against infections. To optimize immune responses, LN stromal cells (LNSCs) produce specific guidance cues (e.g. chemokine), forming unique niches that guide the movement and interaction of immune cells within the LN. Our study showed that LNSCs undergo remodelling during skin inflammation. This remodelling resulted in compromised host immune protection, prolonged S. aureus infection, and increased bacteria systemic dissemination compared to control mice with healthy skin. The goal of this project is to unravel the mechanism by which skin inflammation causes remodelling of LNSCs and investigate how to harness LNSCs to improve host immune protection against skin infection. Through investigating the mechanism by which LNSCs reshape the niches of LNs and disturb immune cell migration, this project will determine whether manipulating LNSC remodelling can improve patients' immune protection to skin infection. Knowledge gained from this project will help develop novel approaches for prevention and management of skin infection in skin diseases. It will also establish a platform to study the role of LNSCs in immune regulation in other diseases.