Basophile Granulozyten sind an allergischen Entzündungen und neuro-immunen Interaktionen bei atopischer Dermatitis (AD) beteiligt. In dieser Arbeit wurde erstmals die Transient receptor potential ankyrin 1-Kanal (TRPA1) -Expression in basophilen Granulozyten von nicht-atopischen Spendern und AD-Patienten untersucht. TRPA1 war in beiden Gruppen nachweisbar, jedoch bei AD signifikant erhöht. Kalziumfluss-Assays bestätigten die Kanalaktivität nach JT010-Stimulation, ohne Effekte auf CD203c- oder CD63-Expression. TRPA1 wurde durch IL-3, IL-31, NGFβ und ein saures Milieu verstärkt, nicht jedoch durch erhöhte Temperatur. Immunfluoreszenz von AD-Läsionen zeigte TRPA1-positive Basophile. Zudem wurde eine durch IL-3, IL-33, NGFβ und pH-Modulation beeinflusste TRPA1/Transient receptor potential vanilloid 1 (TRPV1) -Koexpression festgestellt. Diese Ergebnisse unterstreichen die Rolle basophiler Granulozyten und von TRP-Kanälen in der AD-Pathogenese.
Basophil granulocytes contribute to allergic inflammation and neuro-immune crosstalk in atopic dermatitis (AD). In this study, transient receptor potential ankyrin 1 (TRPA1) expression was investigated in basophils from nonatopic donors and AD patients. TRPA1 was detected in both groups but significantly upregulated in AD. Functional assays confirmed channel activity upon stimulation with the agonist JT010, without changes in CD203c or CD63 expression. TRPA1 levels increased after exposure to IL-3, IL-31, NGFβ, or acidic pH, while temperature had no effect. Immunofluorescence of lesional AD skin confirmed TRPA1-positive basophils. Co-expression with transient receptor potential vanilloid 1 (TRPV1) was shown in basophils and modulated by IL-3, IL-33, NGFβ, and acidic conditions. These findings reveal that basophils express functional TRPA1 and co-express TRPA1/TRPV1, highlighting their potential role in AD pathogenesis.
The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on sensory neurons and immune cells. We hypothesize that TRPV1 plays a role in human eosinophil function and is modulated by inflammatory conditions. TRPV1 expression on human eosinophils was examined by qPCR, flow cytometry, and immunohistochemistry, respectively. TRPV1 functionality was analyzed by investigating calcium flux, apoptosis, modulation by cytokines and acidic pH, and CD69 externalization using flow cytometry. Activation of TRPV1 induced calcium influx and prolonged survival. Although eosinophils were not directly activated by TRPV1 agonists, activation by IL-3 or GM-CSF was mainly restricted to TRPV1-positive eosinophils. TRPV1 surface content was increased by acidic pH, IL-3, IL-31, IL-33, TSLP, TNF-α, BDNF, and NGF-β. Interestingly, TRPV1 was also expressed by eosinophils located in proximity to peripheral nerves in atopic dermatitis (AD) skin. In conclusion, eosinophils express functional TRPV1 channels which are increased by extracellular acidification and AD-related cytokines. Since eosinophils also express TRPV1 in AD skin, our results indicate an important role of TRPV1 for neuroimmune interaction mechanisms in itchy, inflammatory skin diseases, like AD.
International journal of molecular sciences Basel : Molecular Diversity Preservation International, 2000 25(2024), 3, Artikel-ID 1922, Seite 1-15 Online-Ressource
