A Multi-Organ Single-Cell Atlas Maps Allergen and Organ-Specific Cellular Dynamics in the Progression from Food Allergy to Anaphylactic Shock

The transition from food allergic sensitization to life-threatening anaphylactic shock (AS) with complex multi-organ cellular interactions has been poorly understood. We herein conducted a multi-organ single-cell sequencing of heart, lung, and intestinal tissues from mouse models of food allergy, sensitized to bovine serum albumin (BSA) or ovalbumin (OVA), across both sensitization (Phase I) and anaphylactic shock (Phase II). We found that organ-specific pathologies included cardiac vascular dysfunction with pericyte loss and cardiomyocyte adaptation, distinct lung responses (Th2/B-cell predominance with BSA vs. neutrophilia with OVA), and profound intestinal remodeling featuring Paneth cell expansion. We also identified conserved inflammatory pathways (e.g., NOD-like receptor, NF-{kappa}B, JAK-STAT signaling) and unique organ specific signatures. Notably, phase-dependent reprogramming showed NLRP3 inflammasome activation and suppressed anti-inflammatory responses during AS. Cell-cell communication networks shifted from stromal-immune crosstalk in Phase I to dominant myeloid-vascular/neuroimmune interactions in Phase II. We further linked early extracellular matrix remodeling to late-stage neuromodulatory responses in Schwann and smooth muscle cells. This multi-organ atlas elucidates the coordinated, organ-selective immune cascade driving FA to AS progression, providing a foundational resource for developing targeted therapeutic strategies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/703914v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@19ffd9forg.highwire.dtl.DTLVardef@c3fda3org.highwire.dtl.DTLVardef@141174corg.highwire.dtl.DTLVardef@60ac5b_HPS_FORMAT_FIGEXP M_FIG C_FIG