Group 2 innate lymphoid cells and CD4⁺ T cells cooperate to mediate type 2 immune response in mice

Background: Innate lymphoid cells (ILCs) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILCs (ILC2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC2s and other immune cells. We sought to investigate the capacity of ILC2s to regulate effector functions of T cells.

Methods: We isolated ILC2s from the lungs of naïve mice. We cultured CD4⁺ T cells with ILC2s in vitro and examined the functions of these cell types. The mechanisms were investigated using blocking antibodies and cells isolated from cytokine-deficient mice. For the in vivo study, we adoptively transferred ILC2s and CD4⁺ T cells into Il7ra ^-/- mice and subsequently exposed the mice to ovalbumin and a cysteine protease.

Results: Lung ILC2s enhanced CD4⁺ T-cell proliferation and promoted production of type 2 cytokines in vitro. The interaction between ILC2s and CD4⁺ T cells involved costimulatory molecule OX40L and cytokine IL-4, which was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4⁺ T-cell populations, but not each population alone, into Il7ra ^-/- mice resulted in induction of a robust antigen-specific type 2 cytokine response and airway inflammation.

Conclusion: Lung ILC2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases.