Nasal Systems Immunology Identifies Inflammatory and Tolerogenic Myeloid Cells That Determine Allergic Outcome Following Challenge

AbstractInnate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. Here, we investigated their role at nasal mucosa following challenge with house dust mite. We combined single cell proteome and transcriptome profiling on immune cells from nasal biopsy cells of allergic rhinitis and non-allergic subjects, before and after repeated nasal allergen challenge. Nasal biopsies of patients showed infiltrating inflammatory HLA-DRhiCD14+monocytes and CD16+monocytes, and transcriptional changes in resident CD1C+CD1A+conventional dendritic cells (cDC)2 following challenge. Importantly, although clinically silent, non-allergic individuals displayed a distinct innate MPS response to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (HLA-DRlowCD14+monocytes), as well as cDC2 clusters expressing increased inhibitory/tolerogenic transcripts. Therefore, we identified not only clusters involved in airway inflammation but also a non-inflammatory, homeostatic blueprint of innate MPS responses to allergens in non-allergic individuals. Future therapies should target innate MPS for treatment of inflammatory airway diseases.Abstract Figure