23 September 2020
Gene expression linked to inflammatory diseases
Published online 17 June 2013
The protein BACH2 is important to the production of antibodies by B-cells. Genetic variation in the gene BACH2 is linked with a range of autoimmune and inflammatory conditions, including asthma, type 1 diabetes and multiple sclerosis.
This led a team of researchers, led by Rahul Roychoudhuri and Nicholas Restifo of the US National Cancer Institute, in collaboration with Francesco Marincola of the Sidra Medical and Research Centre in Doha to probe how BACH2 expression can interfere with the normal functioning of the immune system, reporting their findings in Nature1.
Knockout mice missing the BACH2 gene developed inflamed lungs and gut with activated CD4+ T-cells – signs of autoimmune disease. These specialist immune cells can either activate or inhibit the immune response, depending on their respective differentiation into either effector T (Teff) or regulatory T (Treg) cells. The knockout mice were found to have less of the immune-inhibitory Treg cells, indicating that BACH2 is essential for successful Treg cell production.
Using genomic analyses, the researchers were able to see how BACH2 affects the expression of other genes across the genome. BACH2 favours the development of protective Treg cells by repressing the rise of potentially damaging effector cells, and thereby helping to suppress inflammation.
- Roychoudhuri, R. et al. BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis. Nature (2013) doi:10.1038/nature12199