Rommel, Frank R.Frank R.RommelTumala, SusanneSusanneTumalaUrban, Anna-LenaAnna-LenaUrbanSiebenhaar, FrankFrankSiebenhaarKruse, JohannesJohannesKruseGieler, UweUweGielerPeters, Eva M. J.Eva M. J.Peters2024-11-202024-11-202024https://jlupub.ub.uni-giessen.de/handle/jlupub/19863https://doi.org/10.22029/jlupub-19218Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.enNamensnennung 4.0 Internationalddc:610