Main Content

Rattay lab

The projects in the laboratory cover the following main research topics:

Thymic tissue development, homeostasis and cell-cell communication

Lymphocyte pools are under steady turnover and get constantly replenished by newly developed cells. The progenitors of T-lymphocytes originate from hematopoietic progenitor cells in the bone marrow and traffic to the thymus where they differentiate and undergo maturation and selection (i.e., positive and negative selection). Proper thymus function essentially depends on cell-cell interactions between different cell types:

I.       Between T-lymphocyte progenitors and endothelial cells during immigration from the blood into the stroma

II.      Between developing T-lymphocytes and epithelial cells (medullary and cortical, mTECs and cTECs, respectively) and dendritic cells (DCs) for positive and negative selection

III.     Between T-cells and endothelial cells for egress into the blood

The research group aims at elucidating the cellular and molecular mechanisms underlying thymic tissue homeostasis during development and to better understand the crosstalk between the different cell types shaping the efficiency of central tolerance.

Thymic self-peptide repertoire transcription, translation and presentation

Immunological tolerance is essential in order to avoid immune reactions towards self-peptides; namely autoimmune reactions. Central tolerance induction occurs in the thymus mediated by different sets of thymic antigen-presenting cells (APCs) including thymic epithelial cells (i.e., cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs)), dendritic cells (DCs) and thymic B cells.

These thymic APCs present endogenously transcribed and imported peripheral peptides on major histocompatibility complex (MHC) class I and II molecules on their surfaces to developing T cells. When clonotypic TCRs bind to self-antigen/MHC complexes above a certain threshold, the respective auto-reactive T cells will be either purged from the repertoire by deletion or fate-diverted into regulatory T cells. Among these thymic APCs, mTECs stand out due to their ability to promiscuously express the majority of tissue-restricted self-antigens (TRAs) and thus by themselves largely procure self-tolerance against peripheral tissues.

The lab studies the development of mTECs and their different subsets with regards to their role in central immune tolerance induction. The regulatory mechanisms involved in gene expression in mTECs are analyzed in order to better understand the highly complex transcriptional profiles in mTECs and the heterogeneity of the mTEC population.