ILCs in chronic pulmonary infections
Innate lymphoid cells (ILCs) are part of the innate immune system and play important roles as regulators of tissue homeostasis, immunity and inflammation. ILCs are divided in 3 subgroups, named ILC1, ILC2 and ILC3 each taking on different tasks. Even rare in frequency and numbers (0.01 – 0.09 % in blood), ILC2s appear to be important cells in activating type 2 inflammation while residing in mucosal tissues (of lung, intestine and skin) but also circulating in the blood. In certain inflammatory conditions such as COPD, asthmatic disease and so on, ILC2s and its cytokines play a key role in allergic inflammation, but also in epithelial cell repair and control of tissue inflammation linked to pathogens.
Whithin my project, I focussing on following aspects: ILCs in chronic pulmonary diseases as cystic fibrosis (CF) and on activation and homeostasis of ILC2s.
CF is a progressive, genetic disease causing mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein leading to impaired chloride (Cl-) transport. That leads to sticky and sick secretion of fluids in the body that may plug tubes, ducts and passageways and thus causes severe damage to the lungs, digestive systems and other organs. Focussing in the pulmonary aspects, during the development of the disease the inflammatory response is dysregulated in several levels, thus leading to an inefficient microbial clearance and contributing to lung damage. However, the role of ILCs in CF patients has not yet been elucidated. In this project ILC profiles and states will be analyzed in blood and bronchoalveolar lavage (BAL) to get more information about the plasticity of these cells and to provide new information about immune-pathomechanism that may provide hints for new associated treatments.
Furthermore, to obtain a better understanding oft he mechaisms involved in the activation and homeostasis of these cells, ILC2s will be characterized in ex vivo culture experiments by analysing changes in activation markers. Isolated ILC2s are cultured in vitro and stimulated with different combinations of cytokines including common-gamma chain cytokines. Changes in cytokine production are measured by performing intracellular staining as well as surface staining with ILC2 markers for characterization.
(by Sarah Plicht)