Compromised central tolerance of ICA69 induces multiple organautoimmunity

Antonina Coppola, Maria Grupillo, Antonina Coppola, Giulio Gualtierotti, Jing He, Asako Tajima, Gregory Owens, Massimo Trucco, William A. Rudert, Yong Fan, Jing He, Gregory Owens, Suzanne Bertera, Massimo Pietropaolo, Gregory Owens

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing autoimmune responses against other organs/tissues. We identified ICA69, a known b-cell autoantigen in Type 1 diabetes, as a potential common target in multi-organ autoimmunity. NODmice immunized with ICA69 polypeptides exhibited exacerbated inflammation not only in the islets, butalso in the salivary glands. To further investigate ICA69 autoimmunity, two genetically modified mouse lines were generated to modulate thymic ICA69 expression: the heterozygous ICA69del/wt line and thethymic medullary epithelial cell-specific deletion Aire-dICA69 line. Suboptimal central negative selectionof ICA69-reactive T-cells was observed in both lines. Aire-dICA69 mice spontaneously developed coincident autoimmune responses to the pancreas, the salivary glands, the thyroid, and the stomach. Ourfindings establish a direct link between compromised thymic ICA69 expression and autoimmunity against multiple ICA69-expressing organs, and identify a potential novel mechanism for the development of multi-organ autoimmune diseases.
    Original languageEnglish
    Pages (from-to)10-25
    Number of pages16
    JournalJournal of Autoimmunity
    Volume53
    Publication statusPublished - 2014

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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