Vliv autoimunitního regulátoru na protilátkovou odpověď proti TH17 efektorovým cytokinům a kvasince Candida albicans

Liberdová, Jana

The Autoimmune Regulator (Aire) is a well-known master regulator of central tolerance, promoting the expression of antigens restricted to peripheral tissues in the thymus. These antigens are presented to developing T cells, ensuring the elimination of self-reactive clones based on their ability to recognize them. Aire dysfunction leads to the development of multiorgan autoimmune pathologies and susceptibility to chronic mucosal fungal infections. The emergence of autoimmunity is largely explained by the disruption of the thymic regulation of peripheral antigen expression. However, the mechanisms underlying fungal infection susceptibility are much less understood. Mucosal anti-fungal immune defense in general primarily relies on the mobilization of TH17 cells and IgA antibodies. Defective cellular TH17 response and autoantibodies against TH17 effector cytokines observed in Aire deficiency are associated with higher susceptibility to fungal infection. However, the integrity of IgA response in Aire deficiency has not been addressed so far. In my thesis, I confirmed that Aire deficient mice develop elevated levels of autoantibodies against TH17 effector cytokines. These autoantibodies are not affected by experimental fungal colonization, suggesting that active fungal infection is not enhancing the...

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