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, Suzanne Bertera, Massimo Pietropaolo

    Risultato della ricerca: Article

    15 Citazioni (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.
    Lingua originaleEnglish
    pagine (da-a)10-25
    Numero di pagine16
    RivistaJournal of Autoimmunity
    Volume53
    Stato di pubblicazionePublished - 2014

    Fingerprint

    Central Tolerance
    Autoimmunity
    Salivary Glands
    Autoimmune Diseases
    Autoantigens
    Type 1 Diabetes Mellitus
    Pancreas
    Stomach
    Thyroid Gland
    Epithelial Cells
    Inflammation
    T-Lymphocytes
    Peptides

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cita questo

    Coppola, A., Grupillo, M., Coppola, A., Gualtierotti, G., He, J., Tajima, A., ... Pietropaolo, M. (2014). Compromised central tolerance of ICA69 induces multiple organautoimmunity. Journal of Autoimmunity, 53, 10-25.

    Compromised central tolerance of ICA69 induces multiple organautoimmunity. / Coppola, Antonina; Grupillo, Maria; Coppola, Antonina; Gualtierotti, Giulio; He, Jing; Tajima, Asako; Owens, Gregory; Trucco, Massimo; Rudert, William A.; Fan, Yong; He, Jing; Bertera, Suzanne; Pietropaolo, Massimo.

    In: Journal of Autoimmunity, Vol. 53, 2014, pag. 10-25.

    Risultato della ricerca: Article

    Coppola, A, Grupillo, M, Coppola, A, Gualtierotti, G, He, J, Tajima, A, Owens, G, Trucco, M, Rudert, WA, Fan, Y, He, J, Bertera, S & Pietropaolo, M 2014, 'Compromised central tolerance of ICA69 induces multiple organautoimmunity', Journal of Autoimmunity, vol. 53, pagg. 10-25.
    Coppola A, Grupillo M, Coppola A, Gualtierotti G, He J, Tajima A e altri. Compromised central tolerance of ICA69 induces multiple organautoimmunity. Journal of Autoimmunity. 2014;53:10-25.
    Coppola, Antonina ; Grupillo, Maria ; Coppola, Antonina ; Gualtierotti, Giulio ; He, Jing ; Tajima, Asako ; Owens, Gregory ; Trucco, Massimo ; Rudert, William A. ; Fan, Yong ; He, Jing ; Bertera, Suzanne ; Pietropaolo, Massimo. / Compromised central tolerance of ICA69 induces multiple organautoimmunity. In: Journal of Autoimmunity. 2014 ; Vol. 53. pagg. 10-25.
    @article{35a4fb22629646638f4fb8c030021434,
    title = "Compromised central tolerance of ICA69 induces multiple organautoimmunity",
    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.",
    author = "Antonina Coppola and Maria Grupillo and Antonina Coppola and Giulio Gualtierotti and Jing He and Asako Tajima and Gregory Owens and Massimo Trucco and Rudert, {William A.} and Yong Fan and Jing He and Suzanne Bertera and Massimo Pietropaolo",
    year = "2014",
    language = "English",
    volume = "53",
    pages = "10--25",
    journal = "Journal of Autoimmunity",
    issn = "0896-8411",
    publisher = "Academic Press Inc.",

    }

    TY - JOUR

    T1 - Compromised central tolerance of ICA69 induces multiple organautoimmunity

    AU - Coppola, Antonina

    AU - Grupillo, Maria

    AU - Coppola, Antonina

    AU - Gualtierotti, Giulio

    AU - He, Jing

    AU - Tajima, Asako

    AU - Owens, Gregory

    AU - Trucco, Massimo

    AU - Rudert, William A.

    AU - Fan, Yong

    AU - He, Jing

    AU - Bertera, Suzanne

    AU - Pietropaolo, Massimo

    PY - 2014

    Y1 - 2014

    N2 - 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.

    AB - 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.

    UR - http://hdl.handle.net/10447/99951

    M3 - Article

    VL - 53

    SP - 10

    EP - 25

    JO - Journal of Autoimmunity

    JF - Journal of Autoimmunity

    SN - 0896-8411

    ER -