The CXCR3 antagonist NBI-74330 alleviates neuroimmune dysfunction by lowering pro-inflammatory mediator signaling in CD45+ cells of BTBR T+ Itpr3tf/J mice

Introduction Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and is often accompanied by stereotyped behaviors. This study examined the effects of the CXCR3 antagonist NBI-74330 on BTBR T+ Itpr3tf/J (BTBR), an autistic mouse model. Recent research suggests that NBI-74330, a CXCR3 antagonist, could have therapeutic benefits in inflammatory and neurodegenerative diseases. Methods We examined NBI-74330's effects on social behavior, self-grooming, and marble burying in BTBR mice. We also evaluated its impact on IFN-γ, T-bet, IL-17A, RORγt, STAT3, IL-22, and AhR levels in CD45 + spleen cells. We measured mRNA levels of these inflammatory mediators in brain tissue. Results Results showed that NBI-74330 significantly improved social interactions and decreased self-grooming and marble-burying behaviors in BTBR mice without affecting arousal, anxiety, or locomotion. Immunological analysis showed marked reductions in CD45 + IFN-γ + , CD45 + T-bet + , CD45 + IL-17A + , CD45 + RORγt + , CD45 + STAT3 + , CD45 + IL-22 + , and CD45 + AhR + cells. NBI-74330-treated BTBR mice exhibited lower mRNA levels of these proinflammatory mediators. Discussion These findings suggest that NBI-74330 can reduce behavioral abnormalities and immune dysregulation in BTBR mice. To our knowledge, this is the first evidence supporting the potential of the CXCR3 antagonist NBI-74330 as a therapeutic option for autism-like symptoms.