Hannover Medical School,
Department for Ped. Pneumology, Allergy und Neonatology
Phenotype and function of innate lymphoid cells in cystic fibrosis lung disease
Cystic fibrosis (CF) is a heritable inflammatory lung disease with reduced life expectancy. In CF-airways, mucus stasis, infection and chronic microbial colonization promote neutrophilic inflammation and drive progressive lung damage. A hallmark of the CF inflammatory response is an exaggerated cytokine production, suggesting that specific inflammatory pathways may constitute promising targets for immunotherapy in CF patients.
Innate lymphoid cells (ILCs) located in the airway mucosa play a decisive role in the first line defense against lung pathogens as they produce pro-inflammatory cytokines in response to signals from the airway epithelium. We have recently shown that ILCs are producers of the pro-inflammatory cytokine IL17 in human CF lungs. In a murine model of CF-like lung disease, we have found neutrophilic inflammation to be reduced in the absence of ILCs and IL17. We thus hypothesize that in the context of CF, ILCs and ILC-derived cytokines may constitute critical determinants of perpetuated lung inflammation.
In our project in the DFG priority program SPP 1937, we aim at understanding the contribution of ILCs and ILC-derived cytokines to CF pathogenesis. To this end, we are studying ILC composition, phenotype and function in lung tissue from human CF patients as well as in a murine model of CF-like disease (bENaC mice) using advanced deep phenotyping methods like chip cytometry and ssRNA sequencing. Additionally, we are exploring targets for possible therapeutic interventions based on our insight into the role of ILCs in chronic inflammation.
- Albrecht, M., H. C. Chen, P. Preston-Hurlburt, P. Ranney, H. G. Hoymann, J. Maxeiner, V. Staudt, C. Taube, H. K. Bottomly, and Dittrich AM. 2011. T(H)17 cells mediate pulmonary collateral priming, J Allergy Clin Immunol, 128:168-77
- Dittrich AM. Chronic Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: Prevention concepts. 2017 Internist (Berl) 58(11):1133-1141.
- Joean O, Hueber A, Feller F, Jirmo AC, Lochner M, Dittrich AM, Albrecht M. Suppression of Th17-polarized airway inflammation by rapamycin. 2017 Sci Rep. 7(1):15336.
- Albrecht, M, Olawaseun, DI, Pallenberg, S, Braubach, P, Jonigk, D, Warnecke, G, Hansen, G, Dittrich, AM. IL-17A producing lymphocytes in end stage lung disease. 2018 Eur Resp J 2018 52(S62):1119