News

May 2025

Rattay Lab moves to Kiel University and the University Hospital Schleswig-Holstein

September 2024

Research Article on: Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development

The crucial role of thymic epithelial cells (TECs) in T cell maturation, selection, and the establishment of central immune tolerance is well-established. Central to these processes are the self-peptides presented by medullary thymic epithelial cells (mTECs), governed partly by the transcriptional regulator Aire and the transcription factor Fezf2. The intricate stages of mTEC maturation, such as post-Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs, coupled with their diverse gene expression profiles, present a significant challenge in deciphering the additional factors that contribute to transcriptional regulation in these cells. Our research aims to unravel the transcriptional regulators driving mTEC development and self-peptide expression comprehensively and genome-wide. We employed ATAC footprinting analysis as an indirect method to identify key transcription factors influencing mTEC gene expression, further substantiated by ChIP sequencing validation and analysis of conditional knock-out mice. The findings highlight Fezf2 as a pivotal regulator of the newly characterized thymic Tuft cells. Additionally, it was discovered that members of the ELF, ESE, ERF, and PEA3 subfamilies of ETS transcription factors, along with the Krüppel-like family of transcription factors, are instrumental in regulating genes crucial for advanced mTEC development and promiscuous gene expression. This newly identified role of Fezf2 in regulating late mTEC and Tuft-mTEC subsets enhances our understanding of the complex cellular landscape of thymic epithelial cells.

published in Frontiers in Immunology

doi: 10.3389/fimmu.2023.1277365

September 2024

Conference Talk 

at the European Congress of Immunology, Dublin, Ireland, 1st – 4th Sept 2024

S. Lammers, V. Barrera, P. Brennecke, C. Miller, J. Yoon, J. Balolong, M. S. Anderson, S. Ho Sui, L. M. Steinmetz, U. H. von Andrian and K. Rattay

Ehf and Fezf2 regulate thymic tissue homeostasis and thymic tuft cell development

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conference program

May 2024

Conference Talk and Poster Presentation

at the ThymE Meeting, Porto, Portugal, 27th - 31th May 2024

S. Lammers, V. Barrera, P. Brennecke, C. Miller, J. Yoon, J. Balolong, M. S. Anderson, S. Ho Sui, L. M. Steinmetz, U. H. von Andrian and K. Rattay

Transcriptional regulation of late medullary thymic epithelial cell development and thymic tuft cells by Ehf and Fezf2

conference homepage

conference program

March 2024

Review Article on: Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis

The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. In a recent review article these insights are discussed, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the signaling pathways during thymus development are described, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, the review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.

published in Frontiers in Immunology

doi.org/10.3389/fimmu.2024.1339714

March 2023

Review Article on: The Role of Viral Infections in the Onset of Autoimmune Diseases

Autoimmune diseases (AIDs) are the consequence of a breach in immune tolerance, leading to the inability to sufficiently differentiate between self and non-self. Immune reactions that are targeted towards self-antigens can ultimately lead to the destruction of the host’s cells and the development of autoimmune diseases. Although autoimmune disorders are comparatively rare, the worldwide incidence and prevalence is increasing, and they have major adverse implications for mortality and morbidity. Genetic and environmental factors are thought to be the major factors contributing to the development of autoimmunity. Viral infections are one of the environmental triggers that can lead to autoimmunity. Current research suggests that several mechanisms, such as molecular mimicry, epitope spreading, and bystander activation, can cause viral-induced autoimmunity. In the newly published review article (Sundaresan et al. 2023) we describe the latest insights into the pathomechanisms of viral-induced autoimmune diseases and discuss recent findings on COVID-19 infections and the development of AIDs.

The publication can be found here:

https://www.mdpi.com/2202242