Regenerative MedicineIL-18 Blocks Thymus Recovery After Chemotherapy by Activating NK Cells
After chemotherapy, radiation, or infection, the thymus struggles to rebuild itself, leaving patients vulnerable to prolonged immune deficiency. This Nature Immunology study reveals why: tissue damage triggers caspase-1-mediated cell death, releasing the inflammatory cytokine IL-18 inside the thymus. IL-18 then activates resident natural killer (NK) cells, which mistakenly attack thymic epithelial cells — the master regulators of thymus function and T cell production. Mice lacking IL-18 or its receptor showed significantly better thymic recovery after irradiation. Blocking IL-18 with a monoclonal antibody in transplant recipient mice improved thymus cellularity at day 50. The findings identify IL-18 as a brake on immune reconstitution and a potential therapeutic target, with implications for cancer patients receiving hematopoietic cell transplants.
