Figure 2.

ILC2 plasticity in the lungs. In diseases like COPD and upon viral infections, ILC2s, in response to a combination of IL-12 and IL-1β, can transdifferentiate into IFNγ-producing ILC1-like cells. Infection with the migratory helminth, Nippostrongylus brasiliensis, or intraperitoneal IL-25 administration elicits the proliferation of IL-25-responsive intestinal iILC2s, which upregulate S1P receptors and can migrate to systemic sites such as the lungs. These iILC2s have the ability to produce IL-17 in response to Th17-like culture conditions, consisting of TGF-β, IL-1β, IL-23, and IL-6. Other mechanisms have been described by which ILC2s can produce IL-17 in a RORγt-independent manner under the influence of systemic IL-33 or allergen administration. In Th2-high asthma and CRSwNP, ILC2s are conventional players involved in IL-5 and IL-13 production and can interact with eosinophils. However, in cystic fibrosis and possibly Th2 low asthma, ILC2s have the ability, in response to IL-1β, IL-23, and TGF-β, to differentiate into ILC3-like cells that no longer produce IL-5 but retain the capacity to produce IL-13 and IL-17, and in this manner contributes to the neutrophilic inflammation observed in these types of diseases. Created with Biorender.org.