Integrin β3 Deficiency Unleashes Spontaneous Pulmonary Inflammation by Promoting B Cell Hyperactivation via the CD40-CD40L Axis

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.