About us

Who are we?

The TRR 355 connects researchers across Germany with diverse sets of expertise, all sharing a passion for the Treg cell cosmos. Our consortium highly fosters collaborations between single projects and builds the foundation of a standardized and interactive research network. Scientists from universities and institutions in Mainz, Munich, Kiel and Braunschweig bring along their know-how and perspectives, embracing together our concerted effort to enlighten the power of Treg cells and Treg cell-based therapies.

What are Treg cells?

One of the major concepts in immunology is the discrimination of self versus non-self in order to prevent autoimmunity and allow tolerance. For this, immune cells undergo a learning process in the bodies school, which is located in the thymus. To prevent unwanted reactivity against healthy tissue, self-reactive immune cells become inactive or removed during this education phase. In addition to this ‘recessive’ mechanism of tolerance, the concept of ‘dominant tolerance’ was discovered in the early 90s:

A novel population of CD4⁺ suppressive T cells was identified, which was later referred to as regulatory T cells (Treg cells). By using different modes of action Treg cells are able to downregulate and even 'kill' effector T cells (Teff cells). Nowadays we know that the majority of Treg cells originate from the thymus during a process called central tolerance induction. Besides these thymic-derived tTreg cells also peripherally-induced pTreg cells exist, which develop in the gut-draining lymph nodes and which complement the Treg cell repertoire to confer tolerance to food- and microbiota-derived antigens.

Although all Treg cells share key features of a common identity, their phenotypes and molecular hallmarks greatly vary depending on their localization. We are only beginning to understand how subset-specific molecular programs translate into a functional specialization of Treg cells in distinct microenvironment. Besides their classical immune-regulatory properties, it is now becoming increasingly evident that Treg cells in addition exert important functions in tissue homeostasis and regeneration.

What do we add to the field?

The fundamental role of ‘bulk’ Treg cells in immune homeostasis is well established. Our central rationale is to have a closer look into Treg cell diversity.

• We analyze Treg cell phenotypes on the organismal level by comparing human versus mouse Treg profiles
• We exploit the influence of anatomic locations by analyzing environmental cues that shape Treg cell heterogeneity
• We investigate the influence of cellular interactions, in particular the communication between Treg cells and myeloid cell populations
• We zoom into the Treg cells and explore the importance of different signaling mediators, especially NF-κB signaling molecules, on the Treg cell transcriptomic and functional profiles

We investigate Treg cell heterogeneity on different organizational levels – from cross-species comparison (organismal level) to niche-specific determinants (tissue level) to cellular interaction cues (cellular level) to signaling mediators (subcellular level)

Across all these levels we further interrogate how deviations from the healthy situation impact Treg cell development, maintenance and function by applying different disease models. We have established different model systems affecting the central nervous system, the muscle, the gut, or the lung across our TRR 355 locations. Our wide expertise in genetic approaches, multi-color flow cytometry and advanced imaging together with our centralized and standardized ‘omics’ project allow us to generate a spatial overview of Treg cell phenotypes on a single-cell level and to furthermore integrate this data with Treg cell functionality.

We believe that creating these datasets is an indispensable prerequisite for future therapeutic approaches. It is envisioned that these strategies will permit the tailored targeting of Treg cells in a tissue-specific manner in order to interfere with disease- and organ-specific autoimmunity/inflammation or to support tissue regeneration while leaving immune surveillance intact.

To address the heterogeneity and functional specialization of Treg cells across different organizational levels, we have assigned our projects to three project areas.

Project Areas

Unraveling the heterogeneity and functional specialization of Treg cells requires a deep understanding of temporally and spatially modulated physiological processes. Any of the participating projects of the TRR 355 is focused on specific perspectives on these intricately linked aspects. The temporal component of Treg cell specialization is dictated by developmental processes in health (homeostasis) and disease. Therefore, we categorized the individual projects into:

Project Area A: Projects related to steady state scenarios
Project Area B: Projects dealing with disease situations
Project Area Z: Service projects providing technical and administrative power

Nonetheless, it is important to point out that health and disease are plastic states rather than fixed traits of a given anatomical or functional niche, so that the classification of individual projects into homeostatic or disease-associated scenarios aligns our projects on a continuum rather than in truly distinct categories.