Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-Cell tolerance

Naoko Wada, Koji Nishifuji, Taketo Yamada, Jun Kudoh, Nobuyoshi Shimizu, Mitsuru Matsumoto, Leena Peltonen, Seiho Nagafuchi, Masayuki Amagai

研究成果: Article査読

37 被引用数 (Scopus)

抄録

In the mechanism of thymus-induced central tolerance, the transcription factor Aire has been demonstrated to promote the expression of a wide range of peripheral organ-specific antigens (Ags) in the medullary thymic epithelial cells (mTECs), which serve as self-Ags in negative selection. We examined the expression of desmoglein 3 (Dsg3), the autoantigen in pemphigus vulgaris (PV), in mouse thymus and the involvement of Aire in tolerance to Dsg3. Immunofluorescence and in situ hybridization revealed Dsg3 in single cells or in clusters in 3% of mTECs near the cortico-medullary junction of the thymus in C57BL/6 mice. Dsg3-expressing mTECs also expressed some Ags of skin-unrelated peripheral organs simultaneously. In contrast, Dsg3-positive mTECs were not detected in the Aire +/+ thymus. Adoptive transfer of splenocytes from Aire -/- mice immunized with Dsg3 did not induce anti-Dsg3 IgG production or PV phenotype in Rag2 / recipient mice. However, Aire / CD4 + T cells, but not Aire +/+ CD4+ T cells, induced low levels of anti-Dsg3 IgG production when transferred with Dsg3 / B cells. These findings indicate that Aire has an important role in Dsg3 expression as well as in selection of T cells that help B cells to produce anti-Dsg3 IgG in thymus.

本文言語English
ページ(範囲)410-417
ページ数8
ジャーナルJournal of Investigative Dermatology
131
2
DOI
出版ステータスPublished - 2011 2月
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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