Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a primary metabolic sensor, and is expressed in different immune cells, such as macrophage, dendritic cell, neutrophil, T cell, and non-immune cells, for instance, synovial fibroblast, and islet beta cell. HIF-1 alpha signaling regulates cellular metabolism, triggering the release of inflammatory cytokines and inflammatory cells proliferation. It is known that microenvironment hypoxia, vascular proliferation, and impaired immunological balance are present in autoimmune diseases. To date, HIF-1 alpha is recognized to be overexpressed in several inflammatory autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and function of HIF-1 alpha is dysregulated in these diseases. In this review, we narrate the signaling pathway of HIF-1 alpha and the possible immunopathological roles of HIF-1 alpha in autoimmune diseases. The collected information will provide a theoretical basis for the familiarization and development of new clinical trials and treatment based on HIF-1 alpha and inflammatory autoimmune disorders in the future.