The immune response is composed of a diverse network of defenses, including cellular components and soluble mediators. A proper immune response relies on the innate immunity, characterized by a rapid and nonspecific initial response to infections and later on the adaptive immunity, characterized by a specific response to a particular antigen. Failure of host defense may occur, causing the dysregulation of the immune system, in particular the onset of immunodeficiency, autoimmunity and cancer predisposition.
Primary immunodeficiencies comprise more than 200 different disorders that affect the development and the functions of the immune system. Many scientific papers have been published on the molecular and cellular basis of the immune response and on the mechanisms involved in the correct development of immune system components. Although today the genetic and molecular basis of the principal mechanisms involved in the immune response are well known, some aspect in this field remain unclear.
In this thesis, during the three years of my PhD program, I have contributed to elucidate “Primary Immunodeficiencies: novel insight in pathogenesis and potential therapeutic approach”, through the combination of clinical, cellular, functional and molecular approaches.
In particular, my research work is focused on the deepening of the knowledge on thymic ontogeny, in particular on the study of the functional role of FOXN1 transcription factor in the development of the T-cell ontogeny and new strategy to develop an in vitro thymic organoid.
Moreover, I participate to give a contribution to better define the regulatory mechanisms of the immune system, with particular regard to the central and peripheral tolerance, whom impairment function leads to autoimmunity.
Finally, I also participated to better define the role of the immune system genes, whom alteration induce the development of cancer predisposition, endocrine system failure and neurodegeneration. In particular I studied the role of gc in cell cycle progression, strongly related to its cellular amount and GH-R signaling, defining the basis of the physiological interaction between endocrine and immune systems, and the role ATM in the progressive neurological dysfunction.
Overall, all my studies were designed in order to clarify unsolved issues and unknown mechanisms underlying the functionality of the immune system. These results could be useful both in the clinical practice and in the basic research of immunedysregulation
