Abnormal T-Cell Development in the Thymus of Non-obese Diabetic Mice: Possible Relationship With the Pathogenesis of Type 1 Autoimmune Diabetes

Author(s)

Mendes-da-Cruz, Daniella A. ^{[1, 2]} ; Lemos, Julia P. ^{[1, 2]} ; Passos, Geraldo A. ^{[3, 4]} ; Savino, Wilson ^{[1, 2]}

Affiliation

^[1] Fundacao Oswaldo Cruz, Oswaldo Cruz Inst, Lab Thymus Res, Rio De Janeiro - Brazil

^[2] Fundacao Oswaldo Cruz, Natl Inst Sci & Technol Neuroimmunomodulat, Oswaldo Cruz Inst, Rio De Janeiro - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto - Brazil

• Document type: Review article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 9, JUL 12 2018.
• Web of Science Citations: 3

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of insulin-producing cells in the pancreas, by direct interactions with autoreactive pancreas infiltrating T lymphocytes (PILs). One of the most important animal models for this disease is the non-obese diabetic (NOD) mouse. Alterations in the NOD mouse thymus during the pathogenesis of the disease have been reported. From the initial migratory disturbances to the accumulation of mature thymocytes, including regulatory Foxp3(+) T cells, important mechanisms seem to regulate the repertoire of T cells that leave the thymus to settle in peripheral lymphoid organs. A significant modulation of the expression of extracellular matrix and soluble chemoattractant molecules, in addition to integrins and chemokine receptors, may contribute to the progressive accumulation of mature thymocytes and consequent formation of giant perivascular spaces (PVS) that are observed in the NOD mouse thymus. Comparative large-scale transcriptional expression and network analyses involving mRNAs and miRNAs of thymocytes, peripheral T CD3(+) cells and PILs provided evidence that in PILs chemokine receptors and mRNAs are post-transcriptionally regulated by miR-202-3p resulting in decreased activity of these molecules during the onset of T1D in NOD mice. In this review, we discuss the abnormal T-cell development in NOD mice in the context of intrathymic expression of different migration-related molecules, peptides belonging to the family of insulin and insulin-like growth factors as well as the participation of miRNAs as post-transcriptional regulators and their possible influence on the onset of aggressive autoimmunity during the pathogenesis of T1D. (AU)

• FAPESP's process: 13/17481-1 - The function of the AIRE gene and of Micro RNAs in the control of adhesion between medullary thymic epithelial cells with thymocytes
• Grantee: Geraldo Aleixo da Silva Passos Júnior
• Support Opportunities: Regular Research Grants