Immune cells with a dual role: switching between protection and attack

As part of the innate immune system, dendritic cells are part of the body's first line of defense against infections. They recognize pathogens and coordinate the immune response. An international team led by ProfessorBarbara Schraml from LMU's Biomedical Center has now comprehensively investigated a new type of dendritic cell and uncovered its important role in the immune response.

As the researchers show, dendritic cells characterized by the expression of the transcription factor RORγt - so-called RORγt+ dendritic cells (DCs) - are found in many tissues. Moreover, they have been conserved across many species over the course of evolution, suggesting that they have essential functions. "We already knew that these cells keep the immune system in balance and prevent overreactions," explains Schraml. "However, we have now discovered that they also act flexibly and can actively trigger immune reactions. They therefore appear to play a crucial role in our immune system."

Role reversal for inflammation

Under normal conditions, RORyt+ DCs help prevent the immune system from attacking harmless targets such as the gut microbiota or food components. However, when infection or inflammation occurs, they can switch roles and activate other immune cells. According to the authors, it is particularly interesting that these cells also appear to play a role in diseases such as multiple sclerosis: In patients with multiple sclerosis, they take on an aggressive profile, suggesting that they contribute to inflammation in the brain and spinal cord.

The dual functionality of RORγt+ DCs also opens up new therapeutic possibilities: For example, these cells could potentially be used specifically in the future to either slow down an overactive immune system or stimulate the immune system. "For example, they could be a target for therapies to treat autoimmune diseases, to improve vaccines, to support cancer immunotherapy or to treat allergies," explains Schraml.

H. Narasimhan et al.: RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen presenting cells. PNAS 2025