Studium fyziologického významu exprese enterických alfa-defensinů v thymu.

• Main Author: Dobeš, Jan
• Other Authors: Filipp, Dominik
• Format: Dissertation
• Language: English
• Published: 2011
• Online Access: http://www.nusl.cz/ntk/nusl-312735

Enteric α-defensins belong to a superfamily of antimicrobial peptides representing the humoral branch of innate immunity. They are produced by intestinal Paneth cells and play an irreplaceable role in the homeostasis of small intestine by modulation of its bacterial composition and the protection of intestinal stem cells residing in the intestinal crypts. Unexpectedly, the tissue-specific gene expression screening of enteric alpha-defensins on a panel of rat tissues revealed their presence in the thymus. The characterization of their cellular source pointed to the CD45- MHCII+ AIRE+ medullary thymic epithelial cells (mTECs). The subsequent analysis further confirmed that, analogous to the rat model, mouse enteric α- defensins (cryptdins) are in the thymus expressed exclusively in the mTECs. It is now well established that autoimunne regulator (AIRE)-dependent transcription of peripheral tissue restricted antigens (TRAs) and their presentation by mTECs leads to a deletion of self- reactive thymocytes. This process of negative section represents the central mechanism of immunological tolerance. Predictably, mutations and malfunctioning of AIRE lead to aberrations in the negative selection, occurrence of self-reactive T-cells and subsequent production of autoantibodies against TRAs. Consistent with...