Transplantation of autoimmune regulator-encoding bone marrow cells delays the onset of experimental autoimmune encephalomyelitis.

Abstract

The autoimmune regulator (AIRE) promotes "promiscuous" expression of tissue-restricted antigens (TRA) in thymic medullary epithelial cells to facilitate thymic deletion of autoreactive T-cells. Here, we show that AIRE-deficient mice showed an earlier development of myelin oligonucleotide glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). To determine the outcome of ectopic Aire expression, we used a retroviral transduction system to over-express Aire in vitro, in cell lines and in bone marrow (BM). In the cell lines that included those of thymic medullary and dendritic cell origin, ectopically expressed Aire variably promoted expression of TRA including Mog and Ins2 (proII) autoantigens associated, respectively, with the autoimmune diseases multiple sclerosis and type 1 diabetes. BM chimeras generated from BM transduced with a retrovirus encoding Aire displayed elevated levels of Mog and Ins2 expression in thymus and spleen. Following induction of EAE with MOG(35-55), transplanted mice displayed significant delay in the onset of EAE compared with control mice. To our knowledge, this is the first example showing that in vivo ectopic expression of AIRE can modulate TRA expression and alter autoimmune disease development.

• Authors: Hyun-Ja Ko, Sarah A Kinkel, François-Xavier Hubert, Zeyad Nasa, James Chan, Christopher Siatskas, Premila Hirubalan, Ban-Hock Toh, Hamish S Scott, Frank Alderuccio
• Journal: European journal of immunology (Eur J Immunol) Vol. 40 Issue 12 Pg. 3499-509 (Dec 2010) ISSN: 1521-4141 [Electronic] Germany
• PMID: 21108470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Autoantigens
• Glycoproteins
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments
• Transcription Factors
• myelin oligodendrocyte glycoprotein (35-55)

Topics

• Animals
• Antigen Presentation (genetics)
• Autoantigens (metabolism)
• Bone Marrow Cells (immunology, metabolism, pathology)
• Bone Marrow Transplantation
• Cell Line
• Cloning, Molecular
• Dendritic Cells (immunology, metabolism, pathology)
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, therapy)
• Epithelial Cells (immunology, metabolism, pathology)
• Female
• Glycoproteins (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments (immunology)
• Thymus Gland (pathology)
• Transcription Factors (genetics, immunology, metabolism)
• Transgenes (genetics)
• AIRE Protein