Benutzerspezifische Werkzeuge

Projekt 2

Immune functions of airway epithelium                

                                           

We have shown that airway epithelial cells use TLRs for sensing infectious danger. However, TLRs are strictly regulated at mucosal surfaces to avoid overshooting reactions and to account for the specific needs of pathogen recognition in airways. We could show that bronchial epithelial cells regulate local dendritic cells and T-lymphocytes, thereby establishing a specific, tolerogenic microenvironment. We propose a concept of local immunity that is shaped by non-immune, stromal cells. Research identified constitutive secretion of prostaglandin E2 and glucocorticoids as epithelial mediators that shape the specific microenvironment. We speculate that additional stressors are necessary to switch from a tolerogenic, homeostatic environment towards a reactive one upon true infection. ER stress was identified to be a kind of “second” signal that mediates this function. Recent work focuses on Pseudomonas aeruginosa and its immune-modulatory functions in Cystic Fibrosis.

Selected publications

Mijošek V, Lasitschka F, Warth A, Zabeck H, Dalpke AH, Michael Weitnauer (2016): Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells. J Innate Immun; 8(5):464-78.

Weitnauer M, Mijošek V, Dalpke AH (2016): Control of local immunity by airway epithelial cells. Mucosal Immunol. 9: 287-298.

Weitnauer M, Schmidt L, Ng Kuet Leong N, Muenchau S, Lasitschka F, Eckstein V, Hübner S, Tuckermann J and Dalpke AH (2014): Bronchial epithelial cells induce alternatively activated dendritic cells dependent on glucocorticoid receptor signaling. J Immunol, 193(3):1475-84

Schmidt LM, Belvisi MG, Bode KA, Bauer J, Schmidt C, Suchy MT, Tsikas D, Scheuerer J, Lasitschka F, Gröne HJ, Dalpke AH (2011). Bronchial epithelial cell-derived prostaglandin E2 dampens the reactivity of dendritic cells. J Immunol 186(4): 2095-2105

Mayer AK, Bartz H, Fey F, Schmidt L, Dalpke AH (2008). Airway epithelial cells modify innate and adaptive immune responses by inducing an anti-inflammatory microenvironment. Eur J Immunol 38(6): 1689-1699