P46 Mast cells block antigen-specific cutaneous immunity in older adults

Abstract Introduction and aims Ageing is associated with increased number and frequency of skin infections and malignancies. This is due in part to profound alterations in immunity termed immunosenescence. Older adults have reduced memory T-cell recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. To date, our research has focused the contribution of T cells and mononuclear phagocytes to impaired cutaneous immunity. Yet the contribution of other innate cell populations to age-associated defective immunity is less well understood. The aim of this study was to utilize multiplex imaging technologies to determine which immune cells contribute to defective cutaneous immunity in older patients. Methods For this study, 5-mm skin sections were collected from normal (unmanipulated) and VZV-challenged younger (< 40 years) and older adults (≥ 65 years). Frozen sections were stained for immune markers and analysed using the CellDIVE imaging platform and assessed using HALO AI analysis software. Results Mast cells were significantly elevated in normal skin of older as compared with younger adults. In VZV-injected skin sections, there were significantly more mast cells in older injected skin as compared with young, which resulted in a significant shift in the ratio of T cells to mast cells. Treatment of older adults with a p38-MAPKinase inhibitor (Losmapimod; 4 days) significantly reduced mast cells while restoring antigen-specific immunity. Conclusions Age-associated accumulation of mast cells in the skin impairs antigen-specific immunity. These data propose that mast cells are a novel therapeutic target to improve antigen-specific immunity in older adults.