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- Title
Autoimmune regulator gene, Aire, is involved in central tolerance to the DM20 isoform of proteolipid protein and the prevention of autoimmune inflammation.
- Authors
Tagawa, Asako; Aranami, Toshimasa; Matsumoto, Mitsuru; Yamamura, Takashi
- Abstract
Objective To show the role of the autoimmune regulator ( Aire), a gene expressed in medullary thymic epithelial cells (m TEC), in the tolerance to encephalitogenic myelin epitopes. Methods C57BL/6J Aire-deficient and wild-type mice were immunized with myelin oligodendrocyte glycoprotein peptide ( MOG35-55) or proteolipid protein peptide ( PLP178-191). PLP178-191 is contained only in PLP/ DM20, an isoform derived from a splice variant of PLP. We evaluated the development of experimental autoimmune encephalomyelitis ( EAE) and reported the T cell response to these peptides. Results m TEC from wild-type mice expressed PLP/ DM20, but those from Aire-deficient mice only expressed it at low levels. Immunization with PLP178-191 induced more severe EAE in Aire-deficient mice than in the wild-type mice. In contrast, MOG35-55 induced EAE of a similar grade in the wild-type and Aire-knockout mice. In recall response assays to PLP178-191, T cells from Aire-deficient mice produced significantly more interleukin ( IL)-17 and interferon ( IFN)-γ than the wild-type mice did. Adoptive transfer of CD4+ T cells purified from PLP178-191-immunized Aire-deficient mice induced a more severe EAE than a similar transfer from the immunized wild-type mice. In comparison with wild-type mice, we also found that sera from aged, naive Aire-deficient mice showed higher titers of PLP178-191-, but not MOG35-55-specific immunoglobulin G autoantibodies. Conclusion Aire is involved in establishing central tolerance to PLP178-191, but not to MOG35-55, and its deficiency induces spontaneous autoreactivity to PLP178-191.
- Subjects
HUMAN genes; AUTOIMMUNITY; AUTOIMMUNE disease prevention; PROTEOLIPIDS; THYMUS
- Publication
Clinical & Experimental Neuroimmunology, 2014, Vol 5, Issue 3, p304
- ISSN
1759-1961
- Publication type
Article
- DOI
10.1111/cen3.12127