Summary
This research project aims to understand the fundamental mechanisms governing the formation, maintenance, and regulation of skin-specific T resident memory cells and their interaction with local tissue Dendritic Cells, applying findings to in vivo mouse models for infection, inflammation, autoimmunity, and protective memory recall.
What they want
The project addresses the urgent need to understand immunity in barrier tissues, specifically focusing on T resident memory cells (TRMs) in the skin. TRMs provide long-term protective immunity against re-encountered pathogens (including CoV2, influenza, herpes, monkeypox, and smallpox) and survey against primary cancers and metastases. However, TRMs can also drive autoimmune memory recall in pathogenic contexts. This proposal tests intervenable regulatory mechanisms involved in the formation, maintenance, and governance of skin-specific TRMs, and their regulatory axis with local tissue Dendritic Cells. The foundational goal is to understand how barrier immunity and T cell receptor repertoire are generated and shaped in tissues like skin. Findings will be applied to in vivo mouse models to test consequences for tissue inflammation, autoimmunity, and protective memory recall, establishing mechanistic groundwork and robust preclinical modeling. The work is also expected to offer basic insight into mechanisms by which immune-modulatory drugs cause tissue-specific toxicities (immune-related adverse events, irAEs) in patients.
Deliverables
- Mechanistic groundwork for skin immunity
- Robust preclinical modeling for infection, inflammation, autoimmunity, and protective memory recall
- Basic insight into foundational mechanisms of immune-modulatory drug toxicities (irAEs)
