CX3CR1-mediated immune networks in sepsis: implications for precision therapy

Sepsis is a life-threatening syndrome characterized by profound immune dysregulation in response to infection, and it remains a major cause of mortality worldwide. The CX3C chemokine receptor 1 (CX3CR1) has emerged as a pivotal regulator of sepsis-induced immune dysregulation, orchestrating the proliferation, differentiation, activation, migration, and survival of various immune cell populations, including monocytes/macrophages, natural killer cells (NK), and T cells. Emerging evidence highlights that the diverse expression patterns of CX3CR1 within distinct immune cell subsets determine its dual pro-inflammatory and anti-inflammatory effects, and CX3CR1 expression level is closely correlated with patient survival in sepsis. In addition, targeted modulation of CX3CR1 in specific immune cell types has shown promising efficacy in preclinical sepsis models. This review provides a comprehensive overview of the molecular immunoregulatory networks governed by CX3CR1, its heterogenous functions across different immune subsets, and recent advances in CX3CR1-targeted therapies, highlighting cell type-specific interventions as promising strategies for precision sepsis treatment.