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  • A Physiological Function of Inflammation-Associated SerpinB2 Is Regulation of Adaptive Immunity

    Author(s)
    Schroder, WA
    Le, TTT
    Major, L
    Street, S
    Gardner, J
    Lambley, E
    Markey, K
    MacDonald, KP
    Fish, RJ
    Thomas, R
    Suhrbier, A
    Griffith University Author(s)
    MacDonald, Kelli P.
    Schroder, Wayne
    Markey, Katrina JI.
    Suhrbier, Andreas
    Year published
    2010
    Metadata
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    Abstract
    SerpinB2 (plasminogen activator inhibitor-2) is widely described as an inhibitor of urokinase plasminogen activator; however, SerpinB2-/- mice show no detectable increase in urokinase plasminogen activator activity. In this study, we describe an unexpected immune phenotype in SerpinB2-/- mice. After immunization with OVA in CFA, SerpinB2-/- mice made 趭fold more IgG2c and generated 貮5-fold more OVA-specific IFN-?-secreting T cells than SerpinB2+/+ littermate controls. In SerpinB2+/+ mice, high inducible SerpinB2 expression was seen at the injection site and in macrophages low levels in draining lymph nodes and conventional ...
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    SerpinB2 (plasminogen activator inhibitor-2) is widely described as an inhibitor of urokinase plasminogen activator; however, SerpinB2-/- mice show no detectable increase in urokinase plasminogen activator activity. In this study, we describe an unexpected immune phenotype in SerpinB2-/- mice. After immunization with OVA in CFA, SerpinB2-/- mice made 趭fold more IgG2c and generated 貮5-fold more OVA-specific IFN-?-secreting T cells than SerpinB2+/+ littermate controls. In SerpinB2+/+ mice, high inducible SerpinB2 expression was seen at the injection site and in macrophages low levels in draining lymph nodes and conventional dendritic cells, and no expression was seen in plasmacytoid dendritic, B, T, or NK cells. SerpinB2-/- macrophages promoted greater IFN-? secretion from wild-type T cells in vivo and in vitro and, when stimulated with anti-CD40/IFN-? or cultured with wild-type T cells in vitro, secreted more Th1-promoting cytokines than macrophages from littermate controls. Draining lymph node SerpinB2-/- myeloid APCs similarly secreted more Th1-promoting cytokines when cocultured with wild-type T cells. Regulation of Th1 responses thus appears to be a physiological function of inflammation-associated SerpinB2; an observation that may shed light on human inflammatory diseases like pre-eclampsia, lupus, asthma, scleroderma, and periodontitis, which are associated with SerpinB2 polymorphisms or dysregulated SerpinB2 expression.
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    Journal Title
    Journal of Immunology
    Volume
    184
    Issue
    5
    DOI
    https://doi.org/10.4049/jimmunol.0902187
    Copyright Statement
    Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
    Subject
    Immunology not elsewhere classified
    Immunology
    Publication URI
    http://hdl.handle.net/10072/35723
    Collection
    • Journal articles

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