Metabolic reprogramming of glutamine is associated with M2 macrophage polarization in allergic rhinitis

Allergic rhinitis (AR) is classically regarded as a type 2 immune-driven disease, yet its chronicity and heterogeneity suggest that additional regulatory layers shape the local immune microenvironment. Although immune cell function is closely linked to metabolic state, how specific metabolic cues are integrated into immune signaling in AR remains unclear.

We combined human nasal mucosal metabolomic analysis, murine models, single-cell transcriptomics, bulk RNA sequencing, and protein assays to investigate the role of glutamine in AR pathophysiology.

We identified elevated glutamine levels in AR nasal mucosa and found that dietary glutamine supplementation was associated with altered nasal behavioral responses in experimental AR. Single-cell profiling revealed changes in immune cell composition, with macrophages displaying a shift toward an M2-like transcriptional state under high-glutamine conditions. Transcriptomic and pathway analyses positioned fibroblast growth factor receptor 1 (FGFR1) within differentially enriched signaling networks, and its expression increased under high-glutamine conditions. Protein-level assays further showed that aminoacylation-associated signals on FGFR1 varied with glutamine availability, together with coordinated changes in YARS and SIRT1.

These hypothesis-generating findings support an associative model in which metabolic alterations in AR are linked to non-canonical modification of FGFR1 and macrophage transcriptional polarization, suggesting a potential immunometabolic layer regulating the nasal mucosal microenvironment.