Experimental Neuroimmunology (ENI)
Cytokines Regulatory T cells Immune cell trafficking Disease monitoring

We are an international research institute at the Technical University of Munich (TUM School of Medicine and Health). At ENI, we conduct basic research to improve our understanding of how immune responses in the central nervous system are initiated and controlled.

Nature (2024)

We are honored to present the newest work from our Institute, published in Nature: In close collaboration with the group of Ludger Klein at LMU, our clinician scientist Ali Afzali and his colleagues revealed a previously unknown mechanism of central tolerance induction for the clinically relevant autoantigen Aquaporin 4 (AQP4), a water channel targeted in the autoimmune disease Neuromyelitis Optica (NMO). For the first time, we could show that a population of thymic B cells was necessary and sufficient to induce tolerance by presenting an endogenous antigen (rather than a BCR-dependently acquired exogenous antigen) to developing T cells. This novel mechanism of negative selection may be malfunctioning in NMO patients, allowing T cells to support anti-AQP4 antibody production in germinal centers. Our study opens up research into the broader role of B cell-associated autoantigens presented in the thymus by the very B cells themselves.

Nature 2024

Sobek Price (2023)

We are proud to announce that our director Prof. Thomas Korn has received the Sobek Price in Multiple Sclerosis Research. He is equally sharing the price with our collaboration partner Prof. Martin Kerschensteiner from the LMU. The price was awarded by the Marga & Mareille Sobek Foundation in Stuttgart on Dec 15 and is the most highly endowed prize for MS Research in Germany. Our contributions to the origins, regulation and temporospatial kinetics of auto-aggressive T cells were highlighted as having a high potential for translational achievements in understanding human MS. We are looking forward to building on these successes with our future projects.

Picture: © AMSEL e.V. / Frank Eppler

Open Positions (2023)

To kickstart work on our recently approved collaborative research grant TRR355 “Heterogeneity and functional specialization of regulatory T cells in distinct microenvironments” we are looking for two further positions in our lab:

1. A new PhD student in T cell immunology (position filled)

2. A full-time lab technician

Both positions can be taken on starting immediately. Application is open now! Please click the respective links for detailed job descriptions and requirements.

Hertie Network of Excellence (2023)

We are happy to report that the charitable Hertie Foundation has announced today that it will extend the Hertie Network of Excellence in Clinical Neuroscience for another 3 years. Following successful evaluation of the program that supports six leading neuroscientific sites (Tübingen, Berlin, Bonn, Hamburg, Heidelberg-Mannheim and Munich) as well as 24 individual fellows working on transregional and translational projects, an additional 6.5 million Euro will be invested into further promoting the scientific progress of brain research.

New funding (2023)

We are proud to announce that another major collaborative research grant for our group has been approved by the German Research Foundation (DFG): The Transregional Collaborative Research Centre (TRR) 355 – Heterogeneity and functional specialization of regulatory T cells in distinct microenvironments – a joint project by TUM, LMU and University of Mainz. The head of our department, Prof. Korn, will be a co-spokesperson alongside Prof. Ari Waisman from Mainz and Prof. Carolin Daniel at LMU.

In TRR355, we will explore the identity, regulation and relevance of regulatory T cells that remain in the central nervous system (CNS) after acute inflammation has subsided. We will establish how their presence and function is related to prolonged adaptive processes, i.e. local immune regulation, tissue recovery and -dysfunction, using mouse models for multiple sclerosis in conjunction with RNA-seq and ATAC-seq technology as well as targeted gene editing in the CNS. We will soon hire new staff to pursue this project.

Proceedings of the National Academy of Sciences (2022)

Our clinician scientists Dr. Meike Mitsdörffer and Dr. Lilian Aly have just concluded their neuroimmunological assessment of glioblastoma tumors, which we have now published in The Proceedings of the National Academy of Sciences. In close collaboration with Dr. Jens Gempt and his colleagues at the Neurosurgery department, we analyzed the leukocyte infiltrate of resected glioblastoma multiforme (GBM) samples donated by patients to elucidate how its composition could explain the widespread resistance to many immune therapies. By subjecting the isolated infiltrates to bulk RNAseq, flow cytometry and detailed histological analysis, we found distinctive signatures and features of Th17 cell commitment among the CD4 T cells, which could indicate unfavorable adaptive immune responses. Our in-depth characterization of these cells opens up new research avenues for different immune modulation strategies.

PNAS, 119(34), 2022

Journal of Experimental Medicine (2022)

We have recently published the project of our researchers Christopher Sie and Ravi Kant in the Journal of Experimental Medicine. Based on the work of our former Postdoc Christian Peter, and in collaboration with further colleagues from our group and the TUM, they showed that IL-24, a cytokine expressed by Th17 cells, can have an unexpected cell-intrinsic effect, independent from its secretion and surface receptor engagement. By modulating the release of the transcription factor Stat3 between mitochondrial and nuclear compartments, intracellular IL-24 can help to induce expression of the regulatory cytokine IL-10. This suggests an autoregulatory mechanism in which Th17 cells, upon continuous inflammatory stimuli, begin expressing IL-24, which in turn limits inflammation via secretion of IL-10.

J Exp Med, 219(8), 2022

Journal of Molecular Medicine (2022)

The work of our clinician scientist Dr. Ali Afzali has been recently published in the Journal of Molecular Medicine. In this project, Dr. Afzali and colleagues addressed the role of Aquaporin-4 (AQP4) in neuroinflammatory processes during a mouse model disease for multiple sclerosis, i.e. MOG-peptide induced experimental autoimmune encephalomyelitis (EAE). AQP4, a water channel expressed in the retina as well as other organs, and best known as the dominant target antigen in the related disease neuromyelitis optica (NMO), still subserved an important function in EAE, despite not being targeted itself in this model. Using mice with genetically disrupted expression of AQP4, we could show that AQP4 is important to maintain retinal ganglion cell survival, possibly by clearing edematous swelling and preventing maladaptive scarring during and following inflammation.

J Mol Med, 100(6): 933-946, 2022

Hertie Network of Excellence (2022)

The Institute of Experimental Neuroimmunology is proud to announce its membership in the Hertie Network of Excellence in Clinical Neuroscience. The network’s goal is to foster interaction between cutting-edge laboratories in Germany, bringing together clinical and scientific expertise to allow faster translational breakthroughs in the treatment of neurological disorders.

It comprises 6 sites (Tübingen, Berlin, Bonn, Hamburg, Heidelberg-Mannheim and Munich) with highly-decorated universities and researchers. The Hertie Foundation is a charity dedicated to promoting brain research and democracy since 1974.

Watch the introduction video for the Hertie network to learn more about our common goal.

Global Immunotalks (2022)

We have the pleasure of contributing to this year’s global immunotalks, a public lecture series featuring state-of-the-art research presented by a selection of leading international colleagues in the field of immunology. All dates and times for 2022 can be found at the UCSD website. You can join via Zoom and find previous recordings on Youtube. Prof. Korn will report on our findings on tissue imprinting of autoreactive T cells at 6 pm (CET) on February 16.

Nature Immunology (2021)

We have recently published the project of our researcher Michael Hiltensperger. In his work, he demonstrates that the site of T cell priming (gut vs. skin draining lymph nodes) dictate their effector phenotype and homing to distal sites of immunopathology. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system in a model of multiple sclerosis are distinct. i-T cells infiltrated white and gray matter, while m-T cells were recruited only to white matter.

Nat Immunol, 22(7): 880-892, 2021

Brain (2021)

We have recently published the work of our clinical scientist Dr. Meike Mitsdörffer. Using a spontaneous mouse model of multiple sclerosis, she showed that meningeal B cell aggregates, previously considered a detrimental component of the chronic pathogenesis in CNS inflammation, can also have an unexpected regulatory function in the disease course. Dr. Mitsdörffer revealed that the formation of these aggregates is dependent on the alpha4-integrin expression of their constituting lymphocytes. Eliminating the B cell aggregates by antibody- or CAR-T-cell treatment exacerbated the disease symptoms. These findings represent an important caveat when developing targeted treatment strategies in the future.

Brain, 144(6): 1697-1710, 2021

Research

The immune system is required to survey the central nervous system (CNS) and protect it from infectious diseases. However, immune surveillance of the CNS is delicate because the brain and the spinal cord do not tolerate immune mediated tissue damage. Uncontrolled adaptive immune responses in the CNS cause serious disease conditions including multiple sclerosis and neuromyelitis optica. It is our aim to characterize the properties of T cells that induce tissue damage in the CNS and to understand how they are regulated. To this end, we pursue four major areas of research as outlined below.

Cytokines

Th1 cells and Th2 cells communicate with other immune cells and are required for host defense against intracellular pathogens and parasites, respectively. In contrast, Th17 cells are different because they communicate with tissue cells and induce severe immunopathology in autoimmune diseases including multiple sclerosis. We have a long standing interest in the differentiation and biology of Th17 cells. IL-6 is a non-redundant factor for the differentiation of Th17 cells, and we have developed tools to investigate the cellular sources of IL-6 and its signaling modalities in the context of the generation of Th17 cells in vivo in animal models for multiple sclerosis.

Regulatory T cells

Adaptive immune responses in the CNS are highly regulated. This regulation takes place by the "re-programming" of pathogenic effector T cells into IL-10 producing T cells but also by "professional" regulatory T cells like Foxp3+ Tregs. In specific anatomical niches (e. g. in the colon) Foxp3+ Tregs can be generated outside the thymus. However, Foxp3+ Tregs that are found in the inflamed CNS are thymus derived (so-called naturally occurring Tregs). We are interested in how these Tregs acquire their regulatory function in the inflamed CNS. We are aiming at understanding whether Tregs in the CNS have functions in tissue homeostasis beyond the regulation of inflammation.

Immune cell trafficking

The provenance of immune cells recruited to the CNS during autoimmune inflammation is not clear. For example, while the gut microbiome has been shown to influence immune responses in distant organs, it is not understood by which mechanisms "environmental cues" imprint certain properties in immune cells and whether these immune cells then physically migrate to distant organs to contribute to tissue homeostasis or induce immune pathology. Here, we are developing genetic tools to mark immune cells site-specifically in order to trace them over short and long periods of time and in various anatomical compartments.

Disease monitoring

Tissue immune monitoring promises to be an excellent means to stratify patients with neuroimmunologic disorders for immune intervention strategies with the most favorable risk/benefit ratio. Using novel imaging technologies including optical coherence tomography (OCT), we aim to better understand the in situ immunologic correlate of distinct imaging signals. We investigate these questions in models of multiple slcerosis and neuromyelitis optica.