GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317568/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317568GEOGSEfalseIntegrin β3 Deficiency Unleashes Spontaneous Pulmonary Inflammation by Promoting B Cell Hyperactivation via the CD40-CD40L AxisBackground: Pulmonary immune homeostasis relies on stringent control of adaptive immunity. Integrin β3 is a critical mediator of cellular adhesion and platelet function. However, its specific role in modulating adaptive immunity, particularly B cell immune response, remains poorly understood.Results: We identified that β3⁻/⁻ mice showed a spontaneous pulmonary inflammation characterized by B cell activation and in situ immune complex deposition in alveoli. Multi-omics integration identified that the CD40-CD40 Ligand (CD40L) axis was strongly implicated in this pathology process. Mechanistically, the absence of β3 potentiates CD40L-CD40 engagement on B cells, leading to hyperactivation of the NF-κB pathway. Notably, reduced ITGB3 expression in patients with autoimmune disease correlated significantly with enhanced transcriptional signatures of B cell activation and inflammation.Methods: Histopathology characterized the pulmonary phenotype of constitutive β3-deficient (β3⁻/⁻) mice. Integrated transcriptomic and proteomic profiling of lung tissue was then performed to map the molecular landscape of spontaneous pulmonary inflammation. Related mechanisms were investigated by histopathology and functional assays, and established clinical relevance by analyzing transcriptomic datasets from patients with autoimmune diseases.Conclusions: Our findings redefine integrin β3 as a threshold regulator of the B cell activation. Consequently, the β3-CD40L-CD40 axis represents a promising therapeutic target for managing B cell-related autoimmune diseases.2026/04/15GSE317568GSM9474297GSM9474286GSM9474296GSM9474295GSM9474294GSM9474293GSM9474292GSM9474291GSM9474290GSM9474289GSM9474288GSM947428724247317568Mus musculus[41953039]