Research

Thymic tissue development, homeostasis and cell-cell communication

Lymphocyte populations undergo continuous renewal and depend on a functional thymus for proper maturation and selection. Progenitor cells originating in the bone marrow enter the thymus, where they differentiate and undergo positive and negative selection. These processes rely on a network of cell-cell interactions:

• Interactions between T-lymphocyte progenitors and endothelial cells during thymic entry
  
  

• Crosstalk between developing T cells and thymic epithelial cells (cTECs and mTECs) and dendritic cells for selection
  
  

• Communication between mature T cells and endothelial cells during thymic egress
  
  

We aim to elucidate the cellular and molecular mechanisms that regulate thymic tissue homeostasis during development and determine how these interactions shape the efficiency of central tolerance.

Thymic self-peptide repertoire transcription, translation and presentation

Central tolerance requires that developing T cells be exposed to a diverse repertoire of self-peptides. Thymic antigen-presenting cells (APCs), including cTECs, mTECs, dendritic cells, and thymic B cells, present endogenously expressed and imported peptides on MHC class I and II molecules.

Binding of TCRs to self-peptide–MHC complexes above a specific threshold leads to clonal deletion or diversion into the regulatory T-cell lineage. Among APCs, mTECs are unique in their ability to promiscuously express tissue-restricted antigens (TRAs), ensuring tolerance to peripheral tissues.

We investigate:

• Developmental pathways of mTEC subsets
  
  

• Transcriptional programs regulating TRA expression
  
  

• Mechanisms controlling mTEC heterogeneity
  
  

• Regulatory networks governing central tolerance

• Cell-cell communication in tissue homeostasis

Methods and technologies

• Single-cell and bulk RNA sequencing
  
  

• ATAC-seq and ChIP-seq
  
  

• Whole-genome expression analysis
  
  

• High-resolution fluorescence microscopy
  
  

• 3D thymic culture systems
  
  

• Flow Cytometry analysis
  
  

• Bioinformatics and computational analyses