Gene critical in heart development protects immune system from ageing

A gene linked to heart development in the embryo also has a role in human immune system function,new research has found.

The CRELD1 gene is known to be involved in embryonic heart development, however, it was previously unknown why the gene continued to be  expressed after birth. Researchers from the University of Bonn, Germany combined transcriptome data from three different studies. Transcriptome analyses, often included in studies on human subjects, are increasingly being shared by researchers who can use the information for work on other unrelated projects. The researchers examined transcriptome analyses which also included immunological data, allowing the correlation between CRELD1 activity and immune function to be made.

'This provided us with information on the activity of the genetic material, including the CRELD1 gene, of a total of 4500 test subjects,' Dr Anna Aschenbrenner from the University of Bonn's LIMES Institute and corresponding author, explained. 'In addition, the data for these participants also included information on certain immunological parameters, such as the number of different immune cells in their blood.'

The study, published in Nature Immunology, confirmed the correlation observed in the transcriptome analyses by conducting CRELD1 knockout experiments in mice. Reduced activity of the CRELD1 gene resulted in a loss of T cells, an important element of the immune response. A similar correlation has been observed in people with an 'aged' immune system and it is hoped that this research will lead to a better understanding of immunological ageing, with a view to slow down or halt the process and reduce the risk of illness in older people.

Immunological ageing or 'immunosenescence' is associated with a characteristic pattern of gene expression in the blood and is mainly found in older people. Dr Aschenbrenner commented, 'We found exactly this signature among participants with low CRELD1 activity'. People affected by immunosenescence are at much higher risk of infection, as is currently seen with COVID-19, and also from age-related diseases such as cancer and Alzheimer's. It may be noted, however, that the immune system can age at various rates and as such, older people may possess a much younger immune system and vice versa.

As immunosenescence is also determined by environmental factors, further studies investigating the expression of CRELD1 in tandem with environmental effects are required. These initial findings, however, provide an encouraging prospect to better understand the cause of immunological ageing.