Ticam2, also known as TRAM, is an adaptor protein in the TLR signaling pathways. It plays a crucial role in mediating pro-inflammatory responses following the activation of Toll-like receptors (TLRs), especially in the context of responses to pathogen-derived stimuli [3]. The TLR-mediated signaling pathways that Ticam2 is involved in are essential for the body's immune defense against invading pathogens [3].

In murine models, Ticam2 has been shown to be involved in neutrophil exhaustion. TICAM2-deficient neutrophils have decreased expression of inflammatory adhesion molecules (ICAM1, CD11b) and immune-suppressors (PD-L1), as well as reduced aggregation following prolonged lipopolysaccharides (LPS) challenge compared to wild-type neutrophils. Ticam2-deficient mice are also protected from developing severe systemic inflammation and multi-organ injury after chemical-induced mucosal damage [1]. Additionally, in a cecal slurry injection sepsis model, Ticam2 -/- mice showed that Ticam2 ablation facilitates monocyte exhaustion recovery after sepsis. Genome-wide DNA methylation analysis in bone marrow monocytes of Ticam2 -/- mice revealed a unique profile of altered methylation at CEBPE binding sites and regulatory features for key immune genes [2].

In conclusion, Ticam2 is an important adaptor protein in TLR signaling pathways. Model-based research, especially using Ticam2 knockout mouse models, has revealed its role in neutrophil and monocyte exhaustion, which are associated with severe systemic inflammation and sepsis. Understanding Ticam2's functions provides insights into the mechanisms of these disease conditions and may offer potential therapeutic targets.