Microglial IL-27 modulates depressive symptoms induced by postnatal immune activation

Genetic or pharmacological inhibition of Trem2 abolishes the antidepressant effects of IL-27, confirming the functional importance of this axis. These findings uncover a previously unrecognized IL-27–STAT1–Trem2 signaling axis regulating microglial function and synaptic integrity. Notably, IL-27 treatment also ameliorates behavioral deficits in a prenatal stress (PNS) model, underscoring its broader relevance across early-life adversity paradigms.

Toxicological and immunological assessments demonstrate that IL-27 administration is well tolerated, with no significant adverse effects, supporting its translational viability. Together, these results position IL-27 as a promising immunotherapeutic candidate and drug target for mood disorders associated with neurodevelopmental immune dysregulation.