Trained immunity’s role in kidney disease

The concept of trained immunity has its origins in infectious diseases. Although useful against infections, new evidence suggests that its improper induction can also lead to abnormal inflammation and tissue damage. Researcher(s) Jordi Ochando of the Icahn School of Medicine at Mount Sinai in New York and Raphaël Duivenvoorden of the Department of Nephrology at Radboudumc explain how trained immunity can have detrimental effects in kidney disease and transplantation. They published their review article in Nature Reviews Nephrology on Oct. 17, 2022.

Our immune system consists of innate and adaptive branches, with innate immune cells providing a rapid nonspecific inflammatory response, while adaptive immune cells provide a slower antigen-specific defense against invading pathogens. It was long thought that only the adaptive immune system could develop memory, but research over the past decade has disproved this. Innate immune cells can also develop memory, called trained immunity. This gives innate immune cells, after encountering certain microbes, the ability to adapt their future inflammatory response. To develop this memory, the cells reprogram their energy metabolism and the transcription of inflammatory genes through epigenetic modifications. This allows the innate immune system to better guard against future infections.

In addition to foreign pathogens, there is evidence that the body's own inflammatory signals can also induce trained immunity, which can have adverse effects in for example autoimmune diseases and organ transplantation. In systemic lupus erythematosus and systemic sclerosis, both autoimmune diseases that often cause kidney damage, there is evidence that trained immunity plays a role in aberrant inflammatory activity, thereby promoting disease progression. Moreover, in experimental models of organ transplantation, trained immunity has been associated with the occurrence of acute rejection, and suppression of trained immunity prolongs graft survival.

The concept of trained immunity provides a better understanding of the involvement of the innate immune response in various pathological conditions involving kidney injury. This provides a new framework for the development of therapies and treatment strategies aimed at manipulating the memory of the innate immune system. The article describes what therapies are being developed and what they are targeting.

Read the study here.

Ochando J, Mulder WJM, Madsen JC, Netea M, Duivenvoorden R. Trained immunity — basic concepts and contributions to immunopathology. Nat Rev Nephrol (2022).