The presentation of neuroendocrine self in the thymus: a necessity for an integrated evolution of the immune and neuroendocrine systems.

During evolution, from ancestor thymoids scattered in gill baskets of the lamprey, the first
unique thymus appeared in jawed cartilaginous fishes around 450-500 millions years ago,
concomitantly or shortly after the emergence of recombinase-dependent adaptive immunity.
The major biological function of the thymus is to generate a diverse repertoire of T-cell
receptors that are self-tolerant. The thymus achieves this role by using two complementary
and intimately associated mechanisms: 1) Apoptotic deletion of T-cell clones bearing a TCR
with high affinity for self-antigens presented by MHC proteins on thymic epithelial cells
(TECs) and dendritic cells (DCs); and 2) Generation of self-antigen specific natural regulatory
T (nTreg) cells. Moreover, the escape from thymic central self-tolerance plays a primary role
in the development of autoimmune diseases that are a significant burden for the quality of life
and health care cost. Our new knowledge in thymus physiology and physiopathology is
currently translated into innovative therapeutic strategies against these devastating chronic
diseases.