Projects / Programmes
Genetic factors involved in imunoregulatory cells deficiency in diseases with expansion of CD4-positive Th-1 biased T cell response
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B790 |
Biomedical sciences |
Clinical genetics |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
invariant NKT cells, type 1 diabetes, sarcoidosis, gene expression, real-time PCR, flow cytometry
Researchers (10)
Organisations (1)
Abstract
T-cells with immunoregulatory properties, notably invariant NKT cells, are involved in regulation of Th1 biased CD4 T lymphocyte response and may have a very important role in type 1 diabetes and in sarcoidosis. Loss of immunoregulation by deficiency of those cells could explain amplified and persistent T-cell activity which characterized the initial phase in those two diseases. However, there is no clear data about the possible genetic background for this deficiency. On the other hand animal models suggest that several control genes are involved in differentiation and development of invariant NKT cells. Those genes are sap, fyn, slamf1, ly108 and vdr. For that reason we will clinically analyze in prospective manner the expression of above mention genes in sarcoidosis patients (which is systemic disease) at the start of the disease and then every 3 months for one year by real-time RT-PCR on standardized blood PAXgene samples. Second, we will investigate the expression of the same genes in a control group of healthy subjects in completely the same manner, i.e. every three months for one year. At the same time we will quantify the concentration of blood invariant NKT cells by V?24 in Vß11 TCR staining and microbeads on flow cytometry. The results will be analysed according to the progress or regress of the disease and according to the dynamic in the control subjects. This project should have an important impact on health care in diabetes and sarcoidosis patients by establishing new biomarker approaches and possible target therapy. Better understanding of genetic background also means new target genes for prognostic polymorphisms involved in autoimmune diabetes and sarcoidosis.
Significance for science
The results of this project should enable a new biomarker approach to early diagnosis and monitoring of sarcoidosis, and probably other diseases with increased Th1-biased CD4 T-cell response , preferably through measurement of regulatory iNKT cells, the expression of SAP , Fyn and SLAM genes , and miR-21 , miR-150 and miR-155 microRNA. This project should have also an important impact on possible new target therapy approaches either through promotion of iNKT cells and/or SAP/SLAM gene expression or targeting of the certain microRNA . For this study it was very important that same the patients were prospectively monitored for up to 4 years through the cource of the disease, as well as that all the methodology ether for quantitative monitoring of gene expression in paired samples or microRNA evaluation was validate on well-defined clinical models. These results will also be important for studies of polymorphisms of candidate genes involved in the predisposition to certain immunological diseases, especially in relation to SAP/SLAM gene pathway and for further understanding of the role of regulatory T-cells in different immunotherapy models. Namely, most of knowledge about the function of regulatory cells is derived from a variety of animal experiments and this project further and significantly clarify their role in some important immunological clinical models.
Significance for the country
One of the key meanings of this project is that it introduce and integrate a research of novel expression and microRNA methodologies on clinical samples in the wider region, as in the individual parts of the project we also included partners from Medical Faculties in Croatia and Bosnia and Herzegovina. This integration has enabled us to include a greater number of patients, what was very important for better Slovenia's research competitiveness on a global immunological research scale and furthermore, these connections will be obviously also used in the further projects. In our project we also included several local presentations at professional meetings and that enable us that the latest results of the project and also the expertise has quickly reached the Slovenian professional medical community. Good research results of this project with several important international publications also play an important role in the global promotion of the Slovenia. Such translational studies are also very important for the development of new forms of target therapies. Thus a better understanding of the major regulatory cells in specific immunological disease, and the expression and microRNA background for cellular dysregulation has also a potential economic value for Slovenia, as it may enable the development of new target therapies, their patenting.
Most important scientific results
Annual report
2010,
2011,
2012,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2010,
2011,
2012,
final report,
complete report on dLib.si
