How Interferon Alters T Cell Dynamics in Lupus
July 10, 2024
Systemic lupus erythematosus (SLE) is an autoimmune disease that impacts multiple body systems and is very difficult to treat. Patients with SLE have abnormal immune responses involving both B cells and T cells, producing higher levels of a molecule called interferon that alters the immune response. However, much remains unknown about these alterations. A recent paper published in Nature, titled “Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus,” provides new insights into how interferon may lead to altered types of T cells in patients.
In this study, scientists collected samples from patients with SLE, rheumatoid arthritis (RA), and healthy controls with no inflammatory disease. They compared the types of immune cells found among these three groups. They identified an imbalance of certain types of T cells in patients with SLE that produce a marker called CXCL13. These T cells, known as T-follicular helper (TFH) cells and T-peripheral helper (TPH) cells, support B cells in their production of antibodies. However, in patients with SLE, some of these antibodies are autoantibodies that target the body’s own tissues.
The scientists then sought to determine the factors that normally regulate the amount of TFH and TPH cells. They found that two proteins, AHR and JUN, typically work together with interferon to regulate the balance of these cells. AHR and JUN reduce the amount of TFH and TPH cells produced, while interferon promotes their production. Patients with SLE produce larger amounts of interferon and, therefore, have increased levels of TFH and TPH cells, which can drive disease progression.
This work is exciting because it adds more evidence that targeting interferon may help alleviate some of the damage and symptoms occurring in SLE.
Citation:
Law, C., Wacleche, V.S., Cao, Y. et al. Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus. Nature (2024). https://doi.org/10.1038/s41586-024-07627-2