Most allergies represent exaggerated type II immune responses driven by adaptive Th2 cells. At least, this is what we used to believe it. However, discovery of rare innate cells, referred as innate lymphoid cells (ILCs), is slowly changing our understanding of cellular responses underlying allergies.
It is clear now that in laboratory mice model of allergy, type 2 ILCs (ILC2) contribute significantly and non-specifically [it seems] in sustaining allergy to irritant-allergens.
For example, new study published in Immunity showed that allergen or IL-33 primed ILC2 can maintain "memory" for 4-6 months independent of Th2 cells.
When analyzed ILC2 response to IL-33 or papain in lung tissue, the authors found that ILC2 displayed a typical adaptive-like behavior (expansion, contraction, quiescence).
Importantly, when IL-33 primed mice were challenged with allergen one month later ILC2 showed heighten type II response to allergen (papain) but not to control (saline). This response was "allergen"[protease]-specific but antigen-independent. It is possible that primed ILC2 were responding to IL-33 [or IL-25] released during papain challenge.
Similar data were obtained from mice primed with fungal Aspergillus protease (ASP) allergen and challenged 3.5 months later with papain (but not to saline). Here too, primed ILC2 could be responding [indirectly] to IL-33 or IL-25 released by papain.
In summary, this study showed that at least in mice "primed" innate lymphoid cells retain "heightened" non-specific responsiveness to allergen "long-term" (up to 6 months). This could explain why adaptive TH2 cell targeting immunotherapies may not be fully successful because it ignores contributions from innate cells such as ILC2.