ABSTRACT
Introduction: Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in both innate and adaptive immunity. Emerging evidence indicates that HIF-1α is associated with the inflammation and pathologic activities of autoimmune diseases.
Areas covered: Considering that the types of autoimmune diseases are complicated and various, this review aims to cover the typical kinds of autoimmune diseases, discuss the molecular mechanisms, biological functions and expression of HIF-1α in these diseases, and further explore its therapeutic potential.
Expert opinion: Inflammation and hypoxia are interdependent. HIF-1α as a key regulator of hypoxia, exerts a crucial role in the balance between Th17 and Treg, and involves in the inflammation and pathologic activities of autoimmune diseases. Although there are many challenges remaining to be overcome, targeting HIF-1α could be a promising strategy for autoimmune diseases therapies.
Article highlights
HIF-1α acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions, and plays a crucial role in both innate and adaptive immunity.
HIF-1α directly promotes Th17 development through transcriptional activation of RORγt.
HIF-1α restricts Treg differentiation and function through binding Foxp3 and targeting it for degradation.
HIF-1α is closely associated with the pathogenesis of autoimmune diseases, and HIF-1α may serve as an effective immunotherapeutic target for autoimmune diseases.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.