Immune System Regulator Allows Inflammatory Response While Preventing Autoimmune Attack

The BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2) gene was shown recently to encode for a protein that acts as a master immune system regulator by enabling inflammatory response to disease causing agents on the one hand and by preventing a hyper-inflammatory response and autoimmune attack on the other.

Genetic polymorphisms within a single locus encoding the BACH2 transcription factor are associated with numerous autoimmune and allergic diseases including asthma, Crohn’s disease, celiac disease, vitiligo, multiple sclerosis, and type I diabetes. The BACH2 protein is normally found on the surface of CD4+ T-cells. These cells play a dual role within the immune system with some populations of CD4+ T-cells activating immune responses, while others, regulatory T-cells (Tregs), function to limit immune responses. An in-depth study of how the BACH2 regulatory factor controls the balance between the two types of immune response was conducted by investigators at the [US] National Institutes of Health (Bethesda, MD, USA).

The investigators worked with a genetically engineered mouse line that permitted silencing or activation of BACH2. They found that the loss of the BACH2 gene in CD4+ T-cells caused them to become inflammatory, even in situations that would normally result in the formation of protective regulatory cells. Mice lacking the BACH2 gene generated large numbers of inflammatory cells, and the animals died of autoimmune diseases within the first few months of life. Insertion of the BACH2 gene via gene therapy into BACH2-deficient cells restored their ability to produce regulatory cells.

"Although genes have been found that play specific roles in either inflammatory cells or regulatory cells, BACH2 regulates the choice between the two cell types, resulting in its critical role in maintaining the immune system’s healthy balance," said senior author Dr. Nicholas P. Restifo, an investigator at the [US] National Institutes of Health. "It is apt that the gene shares its name with the famous composer Bach, since it orchestrates many components of the immune response, which, like the diverse instruments of an orchestra, must act in unison to achieve symphonic harmony."

The study was published in the June 2, 2013, online edition of the journal Nature.

Related Links:
[US] National Institutes of Health