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This provides a structural foundation for their long-term survival and functional execution ( 3.3 Intersection of TED-specific activation signals with classical immune pathways Beyond universal amplification signals, macrophage activation in TED undergoes multi-level signal integration regulation, with the TSHR/IGF-1R functional axis constituting a unique pathological pathway distinct from other autoimmune diseases ( In vitro studies confirm that fibroblasts and macrophages in orbital tissue constitutively express TSHR and IGF-1R, with both receptors forming functional complexes on the cell membrane surface ( TSHR stimulating antibodies not only directly induce mild macrophage activation, but more importantly significantly lower the activation threshold of IGF-1R through allosteric regulation ( 4 Dynamic evolution of the macrophage functional state continuum in the pathological process of TED Within the orbital microenvironment, the functional state of macrophages manifests as a dynamic functional continuum rather than a static M1/M2 phenotype

Bibcode:2011JExpB.214.3751G