Immune System Homeostasis Is Partially Modulated by CRELD1 Gene

A genetic disposition that plays a role in the development of the heart in the embryo also appears to play a key role in the human immune system. This is shown by a recent study led by the University of Bonn in Germany. The study was published today in Nature Immunology.

The gene called CRELD1 is known to play an important role in the development of the heart in the embryo and remains active after birth. For what purpose, however, was previously largely unknown. In order to further understand the role of the gene, the team combined transcriptome data from three different studies. "This provided us with information on the activity of the genetic material, including the CRELD1 gene, of a total of 4,500 test subjects," explains lead researcher Anna Aschenbrenner. "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 researchers discovered a surprising correlation when analyzing this information: The 4,500 analyzed test subjects included some in whom the CRELD1 gene was significantly less active for some reason. Interestingly, the blood of these donors was found to contain only very few T cells. 

The team further investigated this relationship in mouse experiments. The results showed that the genetic loss of the Creld1 gene was indeed the cause for the loss of T cells. T cells lacking the Creld1 gene largely lose their ability to propagate and die earlier. "We see similar changes in people with an 'aged' immune system," Aschenbrenner stresses. 

Those affected are much more susceptible to infections, as currently discussed in the context of COVID-19, but possibly also to age-related diseases such as cancer or Alzheimer's. It is known that the activity of numerous genes in the blood is altered in a characteristic way, which experts also refer to as an immunological aging signature. "We found precisely this signature among participants with low CRELD1 activity," concludes Aschenbrenner.