| Receptor | Binding Affinity (KD) | Downstream Signaling Pathway | Functional Outcome | Key Disease Context |
|---|---|---|---|---|
| TLR4/MD2 | 2.39 × 10^-7 M | NF-κB activation; TLR4/MyD88/TRIF signaling; NLRP3 inflammasome and caspase-1/GSDMD activation; in some contexts STING and ER-stress pathways are also engaged | Induces pro-inflammatory cytokines/chemokines, endothelial dysfunction, NET formation, and inflammatory cell death programs including pyroptosis, necroptosis, and ferroptosis | Sepsis, hemorrhagic shock, acute lung injury, ischemia-reperfusion injury, pulmonary fibrosis (pqac-00000027, pqac-00000031, pqac-00000032, pqac-00000033, pqac-00000034) |
| TREM-1 | 11.7 × 10^-8 M (117 nM) | DAP12-Syk-NF-κB signaling; amplification of TLR4-driven inflammatory signaling; promotes PAD4-dependent NETosis | Activates macrophages and neutrophils, amplifies inflammatory mediator release, promotes NET formation and tissue injury | Sepsis, acute lung injury, hepatic and intestinal ischemia-reperfusion injury (pqac-00000027, pqac-00000030, pqac-00000031, pqac-00000033, pqac-00000037) |
| IL-6R | 9.8 × 10^-8 M | STAT3 signaling; in neurons, IL-6Rα/STAT3/Cdk5 and IL-6Rα/PLC/IP3-associated signaling have been reported | Promotes immune tolerance/endotoxin tolerance, increases PD-L1/IL-10/STAT3-associated programs, impairs bacterial phagocytosis; in neural contexts can promote neuroinflammation | Sepsis-associated immune tolerance, neuroinflammation, stroke-related inflammatory responses (pqac-00000027, pqac-00000030, pqac-00000031, pqac-00000034, pqac-00000035) |


*Table: This table summarizes the best-supported extracellular CIRP receptor interactions, including binding affinities, major downstream signaling routes, and disease-relevant functional consequences. It is useful for distinguishing how eCIRP drives inflammation versus immune tolerance through different receptors.*