生体の低酸素応答と病態 : 血管リモデリングにおける転写因子HIF の関与

Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor１（HIF‐１）. Impairment of HIF‐１‐ dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif‐１α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF‐１α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF‐１α.