Oxygen Sensor Protein Can Regulate B-Cell Anti-inflammatory Response in MS, Study Shows
Oxygen sensor proteins can regulate immune B-cell activity, preventing inflammation in autoimmune disorders such as multiple sclerosis, a study reports.
The research, titled “Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease,” was published in Nature Communications. An autoimmune disease is one in which the immune system attacks healthy tissue instead of invaders.
Cells have mechanisms to protect themselves from dangerous situations. This includes low levels of oxygen, which cells use to generate energy.
In low-oxygen situations, the body activates oxygen sensor proteins known as hypoxia-inducible factors to regulate cell activity. While the role of these HIF proteins has been widely explored in T-cells, little has been known about what they do in B-cells.
A team led by researchers at Germany’s Friedrich Alexander University at Erlangen-Nurnberg found that B-cells have very low levels of HIF-2α protein. They also found that levels of another protein in this class, HIF-1α, increases as B-cells are activated.
These findings prompted the researchers to look closer at the role that HIF proteins play in B-cells. To do this, they genetically engineered mice to not have HIF-1α or HIF-2α protein in their B-cells.
Researchers found no significant changes in the HIF-2α knockout mice, suggesting that this protein does not play a major role in B-cells. In contrast, animals lacking HIF-1α had significantly lower levels of a B-cell subpopulation that could produce the anti-inflammatory signaling protein interleukin-10, or IL-10.
Since IL-10 is an important regulator of inflammation in autoimmune diseases, they next explored HIF-1α’s role in mice models of rheumatoid arthritis and multiple sclerosis. In the absence of the sensor protein, the autoimmune diseases progressed faster, they discovered. This suggested that HIF-1α modulates B-cells in a way that triggers an anti-inflammatory protective mechanism.
Scientists have long considered B-cells master mediators of inflammation in autoimmunity. But the new findings show that HIF-1α can regulate this response and prevent it.
“HIF basically acts like a psychotherapist for a certain type of immune cells — the B-lymphocytes,” Aline Bozec, a professor at the university who was senior author of the study, said in a press release.
“Taken together, this study demonstrates the key function of the hypoxia-associated transcription factor HIF-1α in driving IL-10 expression in B-cells, and in controlling their protective activity in autoimmune disease,” the researchers wrote.
The team suggested that activating HIF-1α “through pharmacologic agents may indeed provide a tool to augment the immune regulatory potential of IL-10-producing B-cells with the potential to prevent and/or treat systemic autoimmune inflammatory diseases.”
