Studies of peripheral tolerance in AIRE deficient mice
Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
Autoimmune Polyendocrine Syndrome Type 1(APS I) is a monogenic autosomal recessive autoimmune disorder which is the result of mutations in the autoimmune regulator (AIRE) gene. Symptoms of the disease include circulation of multiple organ specific autoantibodies, which leads to the breakdown of several tissues, including the adrenal cortex and the parathyroid glands. The patients also develop a number of non-endocrine disorders. This study has investigated the peripheral tolerance mechanisms controlled by the AIRE gene in Aire deficient mice, an animal model of the disease. The B cell Activating Factor (BAFF), which is a cytokine involved in B cell survival and growth, is elevated in Aire-/- mice, resulting in an increased release of autoantibodies and B cell proliferation. Therefore the BAFF level differences between TCR-/- and B6 mice was studied, and the results showed significantly higher levels of BAFF in TCR-/- mice. This is not in accordance with earlier studies. ICOS and ICOSL are involved in the activation of follicular T helper cells. The expression of ICOSL on different subpopulations of DC from mice was studied to evaluate the possible influence of AIRE expression on the T cells in the spleen. The results showed that ICOSL is significantly higher expressed in peripheral 33D1+ DCs in Aire-/- mice, showing that AIRE has a role in the over-activation of the follicular T helper cells, which can lead to autoantibody production and inflammation. These results show that AIRE is involved in peripheral tolerance.
Place, publisher, year, edition, pages
2011. , 17 p.
Autoimmunity, Peripheral tolerance, AIRE, APS I, DC, BAFF, ICOSL
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-69269ISRN: LITH-IFM-G-EX--11/2502--SEOAI: oai:DiVA.org:liu-69269DiVA: diva2:425141
Subject / course
Microbiology and Molecular Genetics
UppsokLife Earth Science
Lindmark, Evelina, PhD Student