Epp Kaleviste "Genetic variants revealing the role of STAT1/STAT3 signaling cytokines in immune protection and pathology"

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View all other units

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Date:

27.08.2020 - 15:00

On 27 August 2020 at 15:00 Epp Kaleviste will defend her doctoral thesis „Genetic variants revealing the role of STAT1/STAT3 signaling cytokines in immune protection and pathology“.

Supervisors: Research Professor Kai Kisand (Institute of Biomedicine and Translational Medicine, University of Tartu), Professor Pärt Peterson (Institute of Biomedicine and Translational Medicine, University of Tartu), Research Professor Lili Milani (Institute of Genomics, University of Tartu).

Opponent: professor Tadej Avcin (Department of Allergology, Rheumatology and Clinical Immunology, University Medical Center Ljubljana and Medical Faculty, University of Ljubljana, Slovenia).

Summary

Cytokines are important molecules that aid information exchange between the cells. Research on cytokines has led to the development of effective medication for different autoimmune diseases. This study focuses on two hereditary monogenic diseases. One is caused by pathogenic variants in STAT1 gene, and the other by variants in AIRE gene. Both diseases are characterized by chronic candida infection, impaired cytokine function, and autoimmunity.

STAT1 gain-of-function (GOF) variant causes chronical mucocutaneous candidiasis. STAT1 participates in the cytokine intracellular signaling pathways. STAT1 gene variants analyzed in this study are GOF variants, meaning that the mutated protein has gained additional properties instead of just being disrupted. The current thesis found that the cells from patients with STAT1 GOF variant had exaggerated responses to antiviral cytokines called interferons and that this can explain their susceptibility to autoimmunity. In addition, the signaling through STAT3 was impaired, which is important in the protection against fungal infections.

In addition, the gene variants of interleukin (IL)-27 were analyzed in this thesis, which is associated with protection against type 1 diabetes. The mutated form of the IL-27 protein possessed decreased activity and reduced induction of the expression of STAT1 target genes.

Pathogenic variants in AIRE gene cause an autoimmune polyendocrinopathy syndrome that is characterized by a variety of autoantibodies against different cytokines. IL-22, signaling through STAT3 factor, is necessary in protection against pathogens. This thesis found that IL-22 paucity, caused by autoantibodies, may lead to an impaired barrier function in the oral mucosa of the patients.

The unique features of monogenic diseases are enabling to study the mechanisms of cytokines in the human immune system.

Location:

Ravila 19-1006 (or via videobridge)

URL:

hdl.handle.net/10062/68470

Event category:

Defence

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Epp Kaleviste "Genetic variants revealing the role of STAT1/STAT3 signaling cytokines in immune protection and pathology"

March