Editorial: The regulation of allergic responses by proteolysis: from protease allergens to host proteases modulation

Editorial on the Research Topic The regulation of allergic responses by proteolysis: from protease allergens to host proteases modulationThe initiation and regulation of the allergic response are dependent on proteolytic events mediated by protease allergens, host-cell and environmental proteases (1, 2).The innate sensing of allergens displaying proteolytic activity mediates the production of pro-Th2 cytokines, alarmins and neuropeptides (2).Moreover, protease allergens play a role in the maturation or degradation of other allergens and disrupt the epithelial barrier integrity through the cleavages of cell-cell tight junction proteins (2).For the initiation of T helper responses, any allergenic protein undergoes proteolytic processing in endolysosomal compartments of antigen-presenting cells (APCs).The resulting peptides are subsequently associated with MHC class II molecules for T cell recognition.The fate of this antigen presentation depends largely on the pH stability of allergens.The present research topic aims to extensively review the critical roles of proteases from allergenic sources, microbes, or host cells in shaping the innate and adaptive response leading to allergic reactions.In this research topic collection, four papers have examined some key immune events mediated by proteases as well as the impact of protein stability in the endolysosomal processing of allergens.The narrative mini-review by Jacquet and Soh outlined how environmental factors, protein dynamics, ligand binding, and post-translational modifications affect allergen stability and susceptibility to proteolysis, which are crucial for maintaining their antigenic and allergenic properties.Proteolytic degradation of allergenic proteins in allergen extracts affects the accuracy of allergy diagnosis and the efficacy of allergen immunotherapy.The review focuses on the impact of protease susceptibility of allergens in various environments, such as skin, airways, gastrointestinal tract, and during endolysosomal processing by APCs, on the fate of the allergic response.Additionally, the article also discusses the influence of lipid ligands on the stability of allergenic lipid binding proteins.Apo-and holo-forms of these allergens exhibit different proteolytic susceptibilities, thereby affecting their immunogenicity.Understanding in details proteolytic stability of allergens could pave the way for more effective allergen standardization which is essential for diagnosis and treatment.