TARID: Thymic Abnormalities in Rare Immunological Diseases

Joint Transnational Call 2019 (JTC2019)

TARID: Thymic Abnormalities in Rare Immunological Diseases

Many rare diseases are caused by a malfunctioning immune system attacking the patient’s own tissues, but treatment options are limited by the fact that the origin of such malfunctioning is poorly understood. In the TARID project we study some of these immunological diseases, united by similar pathogenetic events and pathological findings. Common to the diseases we study is an inherited or acquired defect of AIRE-protein that normally works in the thymus organ. In the thymus AIRE takes part in the development and education of T cells, the cells responsible for cellular immunity. Our hypothesis is that when AIRE is lost in the thymus some unknown harmful mechanism allows T and B lymphocytes to collaborate and together create an abnormal response to structures found in other parts of the human body. This response results in production of antibodies reacting to body’s own structures, so-called autoantibodies that are common in rare immunological diseases. We will identify key steps leading to this abnormal response, and aim to find therapeutic targets that can be manipulated to put the brakes on the pathological production of autoantibodies. The results will be tested in an AIRE-deficient animal model and validated in human tissue culture assays and patient samples. Our ultimate goal is to provide information facilitating the development and use of new modes of treatment in rare immunological diseases.

  • Kekäläinen, Eliisa (Coordinator)
    University of Helsinki [FINLAND]
  • Arstila, T. Petteri
    University of Helsinki [FINLAND]
  • Guilloneau, Carole
    Institut national de la santé et de la recherche médicale [FRANCE]
  • Giraud, Matthieu
    Institut national de la santé et de la recherche médicale [FRANCE]
  • Peterson, Pärt
    University of Tartu [ESTONIA]
  • Graca, Luis
    Universidade de Lisboa [PORTUGAL]
  • Academy of Finland (AKA), Finland (Kekäläinen)
  • Academy of Finland (AKA), Finland (Arstila)
  • French National Research Agency (ANR), France (Guillonneau)
  • French National Research Agency (ANR), France (Giraud)
  • Ministry of Social Affairs of Estonia (MoSAE), Estonia
  • The Foundation for Science and Technology (FCT), Portugal