A new study describes the molecular mechanism by which B-lymphocytes are able to regulate inflammation and provide protection against autoimmune diseases. Hypoxia-inducible factor 1 (HIF-1α) is shown to drive expression of IL-10, an anti-inflammatory cytokine, in B cells. The paper describing the study findings is published in Nature Communications.
The body uses sensors to carefully regulate cellular oxygen levels which are activated if oxygen levels decline due to less being available or more being consumed. HIF is known to be a critical oxygen sensor that is activated when oxygen levels fall. The study demonstrated that increased levels of HIF-1α due to a decline in oxygen levels resulted in a reduction in inflammation.
The team created B cell-specific HIF-1α or HIF-2α knockout mice to determine HIFs influence on B cell cytokine production in relation to autoimmune disease. The experiments showed that B cell activation induces upregulation of HIF-1α expression. Removal of B-cell specific HIF-1α impairs IL-10 expression but the same impairment was not observed with HIF-2α removal. In addition, experiments showed that rheumatoid arthritis mouse models with knocked out HIF1-α showed a significant increase in arthritis compared to normal control mice.
The results of the study lay the groundwork for exploring whether targeting HIF is a viable therapeutic approach to treating chronic inflammatory diseases such as arthritis and multiple sclerosis.