Research Division: Myeloid Cell-Driven Immunoregulation

Myeloid Cell-Driven Immunoregulation—a Sub-Division of Immunology

This Sub-Division within the LIT’s research focuses on so-called skin-associated lymphatic tissue (SALT). Its focus is to investigate how antigen-specific immune responses are both induced and regulated in skin-draining lymph nodes. In this context, we concentrate on myeloid cells and adaptive immune responses resulting from interactions between antigen-presenting cells and T cells.

Currently, we seek to characterize the cellular checkpoints that result in the initiation and regulation of T cell-mediated immunity. Of particular interest, is the impact of myeloid subsets in immune regulation and wound healing.

Our goal is to identify exogenous and endogenous mediators that are interfering with checkpoints in immunoregulation. We seek to modulate these immune checkpoints in order to cure immunopathological manifestations such as autoimmune diseases.

Immunomodulation by microbial components

Our immune system is in permanent contact with the body’s specific bacterial milieu. Such bacteria, also known as commensal bacteria, are important for healthy skin to function optimally as a barrier. Under certain circumstances, however, some commensal bacteria can develop resistance to antibiotics and cause fulminant infections.

The aim of this research project is to understand why our immune system detects but tolerates commensal skin bacteria such as Staphylococcus epidermidis, without inducing active defense mechanisms. Our intention is to seek to overcome this immunotolerance in order to achieve protective immune responses against multi-resistant bacteria.

The specific modulation of these tolerance-mediating triggers is also relevant for the development of new targets against chronic autoimmune and tumor diseases.

This project is funded by the Bavarian Ministry of Science and the Arts within the framework of the Bavarian Research Network: ‘New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking’ (bayresq.net).

Myeloid cells and adaptive immunity

SALT is composed of the following main components:

• A complex group of myeloid cell subtypes capable of processing and presenting skin-derived antigens (foreign or self).
• Skin-draining lymph nodes that respond to cutaneous antigens.
• A wide range of specialized T and B lymphocytes with different functions.

In this context we are particularly interested in the characterization of dermal-derived antigens within skin-draining lymph nodes. We will specifically detect and analyze migratory dermal cells within skin-draining lymph nodes, using various mouse models that the LIT has established.

Previous work has demonstrated that certain subtypes of dendritic cells (DC) can induce DC-specific immune responses against pathogens. Using cutting edge methods such as single-cell RNA sequencing and imaging techniques, we aim to decode the cellular mechanisms responsible for the dissection of commensal-derived or pathogen-derived immune responses.

These findings will help us to further clarify the origin and outcome of adaptive immune responses. In addition, myeloid cells with chimeric antigen receptors (CARs) will be developed. CAR-DCs and CAR-macrophages will be used for the acceleration or attenuation of immunopathological processes. These aspects will play a central role in clinical applications where T-cell responses are induced (e.g. vaccination) or modulated (e.g. autoimmunity).