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Indoleamine 2,3-Dioxygenase in Primary Biliary Cholangitis: A Comprehensive Review of its Role, Clinical Applications, and Regulatory Mechanisms

. Muqaddas Qureshi, Hassan Imran Afridi & Ahsanullah Unar


Primary Biliary Cholangitis (PBC), a common autoimmune liver disease, is characterized by persistent inflammation of the small bile ducts. The disease's pathophysiology is multifaceted, encompassing immune dysregulation, genetic and epigenetic factors, influences from the gut-liver axis, biliary epithelial cell damage, and environmental exposure. A key player in the development of PBC is Indoleamine 2,3-dioxygenase (IDO), an essential enzyme involved in the degradation of tryptophan (Trp) via the kynurenine pathway. This review delves into the diverse roles of IDO in various diseases, including infections, autoimmune diseases, and cholestatic liver diseases, underscoring its potential applications in PBC and its role in the IDO pathway in cancer. IDO proteins predominantly function intracellularly, with other enzymes such as IDO-2, IDO-like protein, and proto-IDO, also capable of degrading Trp. The study proposes potential therapeutic interventions using IDO inhibitors and anticancer drugs, which could yield significant antitumor effects. This review accentuates the pivotal role of IDO in PBC and its wider applications in various diseases, underscoring the need for further research and potential therapeutic advancements.


Index Terms- Indoleamine 2,3-dioxygenase (IDO); interferon gamma (IFNγ); primary biliary cholangitis (PBC); interleukin (IL)-4; localized inflammation


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