Natural killer T cells in intracerebral hemorrhage: phase-dependent immune responses and therapeutic implications

BackgroundIntracerebral hemorrhage (ICH) is the most lethal subtype of stroke, yet effective disease-modifying therapies remain limited. Beyond the primary mechanical insult, dysregulated neuroinflammation is thought to be a major contributor to hematoma expansion, perihematomal edema, and secondary neuronal injury.

Natural killer T (NKT) cells, a specialized population of lipid-reactive lymphocytes linking innate and adaptive immunity, have emerged as potentially relevant immunoregulatory contributors to the post-hemorrhagic response.Main bodyThis review summarizes current experimental evidence, together with the still limited clinical data, regarding the biology of NKT cells in ICH, including their development, subset heterogeneity (type I invariant, type II, and regulatory NKT-like programs), and activation through CD1d-restricted lipid antigens and cytokine-driven pathways. Available evidence supports a phase-dependent working model of NKT-cell function in ICH.

In the acute stage, type I iNKT-associated responses may amplify neuroinflammation through IFN-γ- and TNF-α-related signaling, thereby contributing to myeloid activation, blood-brain barrier (BBB) dysfunction, and neutrophil recruitment.