We are an international research group at the Technical University of Munich. The Korn Lab conducts basic research to improve our understanding of how immune responses in the central nervous system are initiated and controlled.

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, published online on 09 March 2021

New & Extended Funding (2020)

We are happy to report that two of our grants, the Transregio TR128 and the CRC1054, have recently been extended for another four years, now entering their third funding periods each. In the TR128, we will continue to elucidate the role of IL-6 in Multiple Sclerosis in collaboration with our partners in Mainz. In the CRC1054, we will now focus on Aqp4-related tolerance mechanisms in models of Neuromyelitis Optica together with several collaborators at the LMU.

Furthermore, our new Transregio TR274 has recently been approved for its first funding period. Here, we will address the role of regulatory T cells within CNS (post-)inflammatory niches in the resolution of adaptive immune responses and tissue regeneration. This Transregio strengthens our cooperation with local institutions (LMU, DZNE, HHZ, MPI) and opens new collaborative avenues towards our colleagues in Göttingen (IMSF, MPI).

New premises & colleagues (2019)

The Kornlab has moved to its new premises in Trogerstraße. Remaining on the TUM clinical campus at Klinikum rechts der Isar, we have entered new offices and significantly increased our laboratory space. The research building 514 will now harbor the Kornlab until the construction of the new MS research facilities is concluded. To make good use of our new environment, we have recruited our new colleagues Tereza Chadimová and Sofia Tyystjärvi.

Journal of Immunology (2019)

We have recently published the project of our researcher Christopher Sie. In his work, he showed that Dendritic cells, unlike T cells, are largely independent from alpha4 integrin (encoded by Itga4) for their accumulation in the central nervous system during a model disease of Multiple Sclerosis, but do dependent on this surface anchor for their population of the intestinal lamina propria.

J Immunol, 203(6): 1417-1427, 2019

Cell Reports (2019)

Our postdoctoral researcher Garima Garg recently identified a Blimp1-dependent pathway that preserves regulatory T cell (Treg) stability in inflamed non-lymphoid tissues. CNS-infiltrating Treg cells maintain their identity due to Blimp1-expression via restriction of Dnmt3a and a resulting hypomethylation of the CNS2 region of the Foxp3 locus. Ablation of Blimp1, in turn, leads to hypermethylation, loss of Foxp3 expression and severe disease.

Cell Rep, 26(7): 1854-1868 e5, 2019

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.