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HMGB1 signals by binding to RAGE to activate T-cell cytokine release and Fas/FasL signal pathway in uveitis. In uveoretinitis, HMGB1 binds RAGE and activates NF-κB, promoting the release of TNF-α, IL-6, ICAM-1, and VCAM-1. HMGB1 also can activate Fas/FasL-mediated signaling. In Behcet's disease, expression of proinflammatory cytokines such as TNF-α, IL-6, and IFN-γ in neutrophils is enhanced by extracellular HMGB1, which acts via the NF-κB pathway.
