Interleukin-5–producing group 2 innate lymphoid cells control eosinophilia induced by interleukin-2 therapy

Interleukin (IL)-2 promotes regulatory T-cell development and function, and treatment with IL-2 is being tested as therapy for some autoimmune diseases. However, patients receiving IL-2 treatment also experience eosinophilia due to an unknown mechanism. Here, we show that patients receiving low-dose IL-2 have elevated levels of serum IL-5, and this correlates with their degree of eosinophilia. In mice, low-dose IL-2–anti-IL-2 antibody complexes drove group 2 innate lymphoid cells (ILC2) to produce IL-5 and proliferate. Using genetic approaches in mice, we demonstrate that activation of ILC2 was responsible for the eosinophilia observed with IL-2 therapy. These observations reveal a novel cellular network that is activated during IL-2 treatment. A better understanding of the cross talk between these cell populations may lead to more effective targeting of IL-2 to treat autoimmune disease. •Tissue resident group 2 innate lymphoid cells are the main cells producing IL-5 and driving eosinophilia in response to low-dose IL-2 therapy.•We described a novel cellular network activated during IL-2 treatment that may lead to a more efficient use of IL-2 in immunotherapy.