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

作者：Schroder Wayne A; Le Thuy T T; Major Lee; Street Shayna; Gardner Joy; Lambley Eleanore; Markey Kate; MacDonald Kelli P; Fish Richard J; Thomas Ranjeny; Suhrbier Andreas^*

来源：The Journal of Immunology, 2010, 184(5): 2663-2670.

DOI：10.4049/jimmunol.0902187

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 CIA, SerpinB2(-/-) mice made approximate to 6-fold more IgG2c and generated approximate to 2.5-fold more OVA-specific IFN-gamma-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-gamma secretion from wild-type T cells in vivo and in vitro and, when stimulated with anti-CD40/IFN-gamma 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. The Journal of Immunology, 2010, 184: 2663-2670.

• 出版日期2010-3-1
• 单位河北医科大学