Autoimmune regulator gene, Aire, is involved in central tolerance to the DM20 isoform of proteolipid protein and the prevention of autoimmune inflammation. Issue 3 (20th June 2014)

• Record Type: Journal Article
• Authors: Tagawa, Asako; Aranami, Toshimasa; Matsumoto, Mitsuru; Yamamura, Takashi
• Is Part Of: Clinical & experimental neuroimmunology. Volume 5:Issue 3(2014)
• Page Start: 304
• Page End: 314
• Publication Date: 2014-06-20
• Subjects: 616.80479
• DOI: 10.1111/cen3.12127
• Languages: English
• ISSNs: 1759-1961

Abstract

<abstract abstract-type="main" id="cen312127-abs-0001"> <title>Abstract</title> <sec id="cen312127-sec-0001" sec-type="section"> <title>Objective</title> <p>To show the role of the autoimmune regulator (<italic>Aire</italic>), a gene expressed in medullary thymic epithelial cells (mTEC), in the tolerance to encephalitogenic myelin epitopes.</p> </sec> <sec id="cen312127-sec-0002" sec-type="section"> <title>Methods</title> <p>C57BL/6J <italic>Aire</italic>‐deficient and wild‐type mice were immunized with myelin oligodendrocyte glycoprotein peptide (MOG<sub>35–55</sub>) or proteolipid protein peptide (PLP<sub>178–191</sub>). PLP<sub>178–191</sub> is contained only in PLP/DM20, an isoform derived from a splice variant of <italic>PLP</italic>. We evaluated the development of experimental autoimmune encephalomyelitis (EAE) and reported the T cell response to these peptides.</p> </sec> <sec id="cen312127-sec-0003" sec-type="section"> <title>Results</title> <p>mTEC from wild‐type mice expressed <italic>PLP</italic>/DM20, but those from <italic>Aire</italic>‐deficient mice only expressed it at low levels. Immunization with PLP<sub>178–191</sub> induced more severe EAE in <italic>Aire</italic>‐deficient mice than in the wild‐type mice. In contrast, MOG<sub>35–55</sub> induced EAE of a similar grade in the wild‐type and <italic>Aire</italic>‐knockout mice. In recall response assays to PLP<sub>178–191</sub>, T cells from <italic>Aire</italic>‐deficient mice produced significantly more interleukin (IL)‐17 and interferon (IFN)‐γ than the wild‐type mice did. Adoptive transfer of CD4<sup>+</sup> T cells purified from PLP<sub>178–191</sub>‐immunized <italic>Aire</italic>‐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 <italic>Aire</italic>‐deficient mice showed higher titers of PLP<sub>178–191</sub>‐, but not MOG<sub>35–55</sub>‐specific immunoglobulin G autoantibodies.</p> </sec> <sec id="cen312127-sec-0004" sec-type="section"> <title>Conclusion</title> <p> <italic>Aire</italic> is involved in establishing central tolerance to PLP<sub>178–191</sub>, but not to MOG<sub>35–55</sub>, and its deficiency induces spontaneous autoreactivity to PLP<sub>178–191</sub>.</p> </sec> </abstract>