Hyperactive immune cells trigger inflammation

Scientists describe an unknown disorder of the immune system: in a separate subset of immune cells from patients with primary immune deficiency, cellular respiration is greatly increased. This cellular metabolic overactivity causes inflammation, as reported by an international research team led by the University of Basel and the University Hospital Basel. Immunology of nature.

The immune system protects us from infections and tumors – a difficult task, especially because we must avoid harming the healthy tissues of the body. However, rare genetic diseases lead to abnormalities of the immune system called primary immunodeficiency disorders (PIDs). One consequence of these disorders is susceptibility to infections, but some tumors and noninfectious inflammation (autoimmune diseases) may also occur more frequently.

The researchers tested the hypothesis that metabolic activity in the immune cells of patients with PID can serve as a biomarker. They based it on the fact that cellular metabolism is a key regulator of immune cell function. In the immune cells of a subgroup of PID patients examined, a key metabolic process – cellular respiration – was indeed significantly increased. During cellular respiration, energy is generated in the mitochondria, the "power plants of the cell".

Increased cellular respiration

Based on this discovery, the researchers were able to decode a new type of pathological mechanism, from the genetic defect to the mitochondria and the return to signal transduction to the nucleus. The increase in cellular respiration was triggered by the hyperactivity of a protein in the respiratory chain. This then signaled the cells to produce inflammatory mediators. With these results, the researchers were able to successfully administer a targeted treatment approved for another indication.

The study was led by Professor Christoph Hess (Department of Biomedicine (DBM) of the University of Basel and University Hospital Basel and CITIID, University of Cambridge) and Professor Mike Recher (DBM, University Basel and the University Hospital Basel).

"This is an example of how patient-based research can help decode the molecular processes responsible for disease," said Christoph Hess. This benefits patients, who can receive more targeted and effective medications with fewer side effects. In addition, information on basic biological processes from the study of rare diseases may also allow new physiopathological considerations for more common diseases.