Allergic inflammation. The mast cells from inflammation to its resolution. Have we found new druggable targets?

The pivotal effector cells of allergic inflammation (AI) are the mast cells and the eosinophils. Mast cells, as activated by IgE-dependent mechanisms via allergens, are the recognized primum movens while eosinophils infiltration and persistence in the inflamed tissue with the mast cells are the recognized features of the late stage and of the chronic outcome of allergy.

During the years we have defined a highly pro-inflammatory cross-talk between these two cells that we have named the “Allergic Effector Unit” (AEU). We found that mast cell/eosinophil interactions result in increased eosinophils chemotaxis, survival, degranulation, cytokine production and in mast cell survival, IgE-dependent and independent degranulation and cytokine production. These effects are mediated by both released mediators (soluble interactions) and by receptor/ligands binding (physical interactions). Prominent players of the activating "physical" AEU are the two activating receptors (ARs)/ligands CD48 and 2B4. Nevertheless, we have also described the presence and functional activity of two inhibitory receptors (IRs), i.e. CD300a and Siglec-7, on mast cells and on eosinophils that can indicate a possible anti-inflammatory or even pro-resolution activity within the AEU and as mediated by mast cells and perhaps by eosinophils.