Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective from a New Mouse Model
| Autor: | Konstantina Alexandropoulos, Anthony J. Bonito, Olivier Herbin, Erica G. Weinstein |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Anti-nuclear antibody
Disease Autoimmune hepatitis Review antinuclear antibodies medicine.disease_cause T-Lymphocytes Regulatory lcsh:Chemistry Mice 0302 clinical medicine autoimmune hepatitis (AIH) medullary thymic epithelial cells (mTECs) lcsh:QH301-705.5 Spectroscopy medullary thymic epithelial cells central tolerance 0303 health sciences Mutation Peripheral tolerance autoimmune polyendocrine syndrome (APS) General Medicine peripheral tolerance 3. Good health Computer Science Applications Hepatitis Autoimmune 030211 gastroenterology & hepatology medicine.symptom Central tolerance Inflammation Thymus Gland Biology Catalysis Inorganic Chemistry 03 medical and health sciences Antigen medicine Animals Physical and Theoretical Chemistry Molecular Biology 030304 developmental biology T-cells Organic Chemistry autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) Epithelial Cells medicine.disease digestive system diseases regulatory T-cells Disease Models Animal lcsh:Biology (General) lcsh:QD1-999 Immunology soluble liver antigen |
| Zdroj: | International Journal of Molecular Sciences, Vol 16, Iss 1, Pp 1980-2000 (2015) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | Autoimmune hepatitis (AIH) is an immune-mediated disorder that affects the liver parenchyma. Diagnosis usually occurs at the later stages of the disease, complicating efforts towards understanding the causes of disease development. While animal models are useful for studying the etiology of autoimmune disorders, most of the existing animal models of AIH do not recapitulate the chronic course of the human condition. In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the high tolerogenic capacity of the liver. Recently, we described a new mouse model that exhibited spontaneous and chronic liver inflammation that recapitulated the known histopathological and immunological parameters of AIH. The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus, the very process thought to inhibit AIH induction by liver-specific expression of exogenous antigens. The mutation led to depletion of specialized thymic epithelial cells that present self-antigens and eliminate autoreactive T-cells before they exit the thymus. Based on our findings, which are summarized below, we believe that this mouse model represents a relevant experimental tool towards elucidating the cellular and molecular aspects of AIH development and developing novel therapeutic strategies for treating this disease. |
| Databáze: | OpenAIRE |
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