c-Maf: The Immune “Brake” Shaping Autoimmune Disease
What Is a Transcription Factor?
A transcription factor is a type of protein that helps control how cells behave by deciding which genes are turned on or off.
Every cell contains the same DNA, but not every gene is active at the same time. Transcription factors bind to DNA and guide the cell on when to make specific proteins. Those proteins then influence how a cell grows, responds to stress, or communicates with other cells.
In the immune system, transcription factors help determine what type of immune cell develops, how strongly it responds to a trigger, and when an immune response should slow down or stop. Because of this role, changes in transcription factor activity can strongly shape inflammation, immune tolerance, and the risk of autoimmune disease.
What Is a Transcription Factor?
A transcription factor is a type of protein that helps control how cells behave by deciding which genes are turned on or off.
Every cell contains the same DNA, but not every gene is active at the same time. Transcription factors bind to DNA and guide the cell on when to make specific proteins. Those proteins then influence how a cell grows, responds to stress, or communicates with other cells.
In the immune system, transcription factors help determine what type of immune cell develops, how strongly it responds to a trigger, and when an immune response should slow down or stop. Because of this role, changes in transcription factor activity can strongly shape inflammation, immune tolerance, and the risk of autoimmune disease.
The transcription factor c-Maf acts like an immune-system “programmer,” helping to decide when immune cells ramp up inflammation versus applying the brakes. However, rather than acting as simply an on/off switch, c-Maf functions more like a dimmer, shaping how immune cells develop and how much inflammation they produce. This new review explains how c-Maf functions as an immune checkpoint, shaping the development and behavior of many immune cell types, including T cells, B cells, innate lymphoid cells, and macrophages, and why that matters for autoimmune disease.
A key role of c-Maf is promoting IL-10, an anti-inflammatory signaling protein that helps calm immune responses once a threat has passed. Through this pathway, c-Maf supports immune tolerance and helps prevent excessive or chronic inflammation. The review also explains how c-Maf influences specific immune cell subsets such as regulatory T cells and follicular helper T cells that play important roles in antibody production and immune regulation.
Disruptions in c-Maf-controlled pathways have been linked to several autoimmune diseases, including inflammatory bowel disease (Crohn’s disease and ulcerative colitis), type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and immune thrombocytopenia (ITP). When c-Maf signaling is altered, the immune system may produce excessive inflammation or fail to properly regulate antibody-driven immune responses.
The authors note that while c-Maf represents a promising target for future therapies, transcription factors are difficult to target directly. In addition, c-Maf can play different roles depending on the disease and immune context, meaning any future treatments would need to be carefully tailored rather than broadly applied.
Citation
Liu, N., Zhang, J., Wang, P., Jin, S., Yang, C., Yan, X., Xu, J., Wang, H., Sun, W., & Xu, D. (2025). Transcription factor c-Maf: a checkpoint that programs autoimmunity. Frontiers in immunology, 16, 1682098. https://doi.org/10.3389/fimmu.2025.1682098