D-dopachrome tautomerase (DDT)

D-dopachrome tautomerase (DDT), also known as MIF-2, is a cytokine and enzyme closely related to macrophage migration inhibitory factor (MIF) in both structure and function[1][2][3][5]. It catalyzes the conversion (tautomerization and decarboxylation) of D-dopachrome to 5,6-dihydroxyindole[1][3][5]. DDT acts primarily as a cytokine, binding with high affinity to the cell surface receptor CD74 and activating signaling pathways such as ERK1/2 MAP kinase, PI3K–Akt, and JNK, leading to proinflammatory gene expression[1][2][5]. In inflammation, DDT amplifies neutrophil recruitment and the inflammatory response; in cancer, DDT is often overexpressed, enhancing tumor cell survival, migration, and angiogenesis[1][2][5]. Neutralization of DDT in animal models reduces inflammatory cytokines and protects against lethal endotoxic shock[2][5]. DDT is also implicated in cardiac physiology, protecting the heart from ischemic injury, and may serve as a biomarker for certain diseases including cancer and sepsis[1][2][4][5]. Although its exact endogenous substrate and physiological functions are still being clarified, DDT is recognized as a target of therapeutic and biomarker interest in human disease.

Other names

D-dopachrome decarboxylaseDDCTMIF-2MIF2D-DTPhenylpyruvate tautomerase II

Neutralizing antibodies reduce inflammation and decrease circulating proinflammatory cytokines in preclinical models[2][5].