Helmholtz Immunology
Our overall vision is the prevention of aberrant immune activation on an individualized level. Furthermore, this platform aims at bringing researchers closer to our work and providing valuable, accessible insight on immunology for all with clear evidence of the impact on society.
Our overall vision is the prevention of aberrant immune activation on an individualized level. Furthermore, this platform aims at bringing researchers closer to our work and providing valuable, accessible insight on immunology for all with clear evidence of the impact on society.
Selected Publications
See all2022 Mucosal Immunology
Antigen-Specific Treg Therapy in Type 1 Diabetes - Challenges and Opportunities
Regulatory T cells (Tregs) are key mediators of peripheral self-tolerance and alterations in their frequencies, stability, and function have been linked to autoimmunity. The antigen-specific induction of Tregs is a long-envisioned goal for the treatment of autoimmune diseases given reduced side effects compared to general immunosuppressive therapies. However, the translation of antigen-specific Treg inducing therapies for the treatment or prevention of autoimmune diseases into the clinic remains challenging. In this mini review, we will discuss promising results for antigen-specific Treg therapies in allergy and specific challenges for such therapies in autoimmune diseases, with a focus on type 1 diabetes (T1D). We will furthermore discuss opportunities for antigen-specific Treg therapies in T1D, including combinatorial strategies and tissue-specific Treg targeting. Specifically, we will highlight recent advances in miRNA-targeting as a means to foster Tregs in autoimmunity. Additionally, we will discuss advances and perspectives of computational strategies for the detailed analysis of tissue-specific Tregs on the single-cell level.
2022 Advaned Materials
Lung fibrosis, one of the major post-COVID complications, is a progressive and ultimately fatal disease without a cure. Here, an organ- and disease-specific in vitro mini-lung fibrosis model equipped with noninvasive real-time monitoring of cell mechanics is introduced as a functional readout. To establish an intricate multiculture model under physiologic conditions, a biomimetic ultrathin basement (biphasic elastic thin for air–liquid culture conditions, BETA) membrane (<1 µm) is developed with unique properties, including biocompatibility, permeability, and high elasticity (<10 kPa) for cell culturing under air–liquid interface and cyclic mechanical stretch conditions. The human-based triple coculture fibrosis model, which includes epithelial and endothelial cell lines combined with primary fibroblasts from idiopathic pulmonary fibrosis patients established on the BETA membrane, is integrated into a millifluidic bioreactor system (cyclic in vitro cell-stretch, CIVIC) with dose-controlled aerosolized drug delivery, mimicking inhalation therapy. The real-time measurement of cell/tissue stiffness (and compliance) is shown as a clinical biomarker of the progression/attenuation of fibrosis upon drug treatment, which is confirmed for inhaled Nintedanib—an antifibrosis drug. The mini-lung fibrosis model allows the combined longitudinal testing of pharmacodynamics and pharmacokinetics of drugs, which is expected to enhance the predictive capacity of preclinical models and hence facilitate the development of approved therapies for lung fibrosis.
2021 Front Immunol.
Antigen-Specific Treg Therapy in Type 1 Diabetes - Challenges and Opportunities
Regulatory T cells (Tregs) are key mediators of peripheral self-tolerance and alterations in their frequencies, stability, and function have been linked to autoimmunity. The antigen-specific induction of Tregs is a long-envisioned goal for the treatment of autoimmune diseases given reduced side effects compared to general immunosuppressive therapies. However, the translation of antigen-specific Treg inducing therapies for the treatment or prevention of autoimmune diseases into the clinic remains challenging. In this mini review, we will discuss promising results for antigen-specific Treg therapies in allergy and specific challenges for such therapies in autoimmune diseases, with a focus on type 1 diabetes (T1D). We will furthermore discuss opportunities for antigen-specific Treg therapies in T1D, including combinatorial strategies and tissue-specific Treg targeting. Specifically, we will highlight recent advances in miRNA-targeting as a means to foster Tregs in autoimmunity. Additionally, we will discuss advances and perspectives of computational strategies for the detailed analysis of tissue-specific Tregs on the single-cell level.
2021 Science Immunology
OAS1/RNase L executes RIG-I ligand–dependent tumor cell apoptosis
There is increasing interest in developing cancer immunotherapies that target the innate immune pathways regulating cytokine production and cell death, but the interplay between these two closely connected processes is not well understood. In mouse and human cancer cell lines, Boehmer et al. demonstrate that cytokine production and apoptosis induced by retinoic acid–inducible gene I (RIG-I) ligands, including 5′-triphosphate RNA (3p-RNA), are two separable events in which RIG-I is required for production of type I interferon but not execution of apoptosis. Mass spectrometry and loss-of-function assays showed that 3p-RNA directly activates OAS1 and RNase L, which promoted translational arrest and depletion of antiapoptotic MCL-1. These results demonstrate that RIG-I–mediated apoptosis involves priming and effector stages, reminiscent of inflammasome activation, both of which could serve as potential targets for cancer immunotherapy.