Funktionelle Defekte von dermalen innate like lymphoid cells type 2 (dILC2) in RAG1-defizienten Mäusen
Functional deficits in dermal innate like lymphoid cells type 2 (dILC2) in RAG1-deficient mice
von Mohamed Saleh
Datum der mündl. Prüfung:2021-12-01
Erschienen:2022-01-04
Betreuer:Prof. Dr. Timo Buhl
Gutachter:Prof. Dr. Ralf Dressel
Gutachter:Prof. Dr. Margarete Schön
Dateien
Name:Doktorarbeit_2020_TB4_MMS5_final_31052021.pdf
Size:1.80Mb
Format:PDF
Zusammenfassung
Englisch
Dermal innate like lymphoid cells type 2 (dILC2) have been studied extensively during the last decade. Innate-lymphoid cells type 2 (ILC2) play a dominant role in inflammatory and allergic diseases in both, mice and human. To study their biology, RAG1-deficient mice are frequently used for two reasons: First, ILC2 are more abundant and second, they do not have any B und T cells supposedly making it easier to observe their functions independent from them. Here, we demonstrate that dermal ILC2 derived from RAG1-deficient mice are differently regulated than WT dILC2. RNA sequencing revealed different regulations in processes related to cytokine-cytokine-receptor interaction, (auto-)immune response and proliferation. Interesintlgy, dILC2 in RAG1-deficient mice show an activated ILC1/ILC3 phenotype. Furthermore, dILC2 respond differently to allergic stress induced by DNFB contact hypersensitivity, decreasing rather than increasing in cell numbers. This effect was stable in adoptiv transfer experiments. Moreover, our data points out higher apoptosis affinity, possibly due to a mixture of both, intrinsic and extrinsic mechanisms. Lastly, RAG1-deficient dILC2 have higher expression of IL-7 receptor and increased proliferation rate. Together, our data shows that RAG1-deficient dILC2 are vastly different in terms of activation, proliferation and apoptosis. Previous existing emulated from RAG1-deficient dILC2 has to be carefully reevaluated.
Keywords: innate-like lymphoid cells type 2, contact allergy, immunity, skin