Arstila Group - Research

The overall goal of our ongoing research is to characterize in detail the origin and consequences of the T cell dysregulation in APECED. Our work on T cell development and homeostasis in healthy donors will contribute to this goal by providing new
information on the pathways likely to affected by the absence of functional AIRE. In particular, the thymic expression of AIRE suggests that the defects in APECED patients arise already during T cell development, a notion strongly supported by murine studies.

Our specific aims are to:

• Analyze the thymic contribution to peripheral dysregulation in APECED.
• Analyze the role of innate proinflammatory signals in triggering and maintaining the abnormal T cell activity.
• Identify the relevant autoantigens recognized by cytotoxic effector cells in APECED patients, and track the antigen-specific response.
• Identify other factors, especially homeostatic cytokines and anti-cytokine autoantibodies, promoting sustained autoreactivity in the patients.

The data will reveal how the abnormal T cell response is induced and sustained, and what is targeted. These questions are also directly relevant to many of the projects pursued by other groups of the program, whether in other autoimmune diseases or in tumor immunology.

The main methods used in our lab include:

• Cell and tissue culture methods
• Multiparameter flow cytometry and cell sorting
• T cell activation assays
• Cytokine Elispot
• EIA
• HLA multimer analysis
• TCR repertoire analysis and deep sequencing
• Murine models and adoptive T cell transfers
• Standard molecular biology techniques