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 Kudo, Nobuyoshi Shimizu, Mitsuru Matsumoto, Leena Peltonen, Seiho Nagafuchi, Masayuki Amagai

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)410-417
Number of pages8
JournalJournal of Investigative Dermatology
Volume131
Issue number2
DOIs
Publication statusPublished - 2011 Feb

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Desmoglein 3
Pemphigus
T-cells
Autoantigens
T-Lymphocytes
Thymus
Thymus Gland
Epithelial Cells
Immunoglobulin G
B-Lymphocytes
Central Tolerance
Cells
Antigens
Adoptive Transfer
Inbred C57BL Mouse
In Situ Hybridization
Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-Cell tolerance. / Wada, Naoko; Nishifuji, Koji; Yamada, Taketo; Kudo, Jun; Shimizu, Nobuyoshi; Matsumoto, Mitsuru; Peltonen, Leena; Nagafuchi, Seiho; Amagai, Masayuki.

In: Journal of Investigative Dermatology, Vol. 131, No. 2, 02.2011, p. 410-417.

Research output: Contribution to journalArticle

Wada, N, Nishifuji, K, Yamada, T, Kudo, J, Shimizu, N, Matsumoto, M, Peltonen, L, Nagafuchi, S & Amagai, M 2011, 'Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-Cell tolerance', Journal of Investigative Dermatology, vol. 131, no. 2, pp. 410-417. https://doi.org/10.1038/jid.2010.330
Wada, Naoko ; Nishifuji, Koji ; Yamada, Taketo ; Kudo, Jun ; Shimizu, Nobuyoshi ; Matsumoto, Mitsuru ; Peltonen, Leena ; Nagafuchi, Seiho ; Amagai, Masayuki. / Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-Cell tolerance. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 2. pp. 410-417.
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