- Summary RORγt + innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt + ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt + ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt + ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44 + RORγt + ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.