A physiological function of inflammation-associated SerpinB2 is regulation of adaptive immunity

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 and Suhrbier, Andreas (2010) A physiological function of inflammation-associated SerpinB2 is regulation of adaptive immunity. Journal of Immunology, 184 5: 2663-2670. doi:10.4049/jimmunol.0902187

Author 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
Title A physiological function of inflammation-associated SerpinB2 is regulation of adaptive immunity
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2010-03
Sub-type Article (original research)
DOI 10.4049/jimmunol.0902187
Volume 184
Issue 5
Start page 2663
End page 2670
Total pages 8
Place of publication Bethesda, MD, United States
Publisher The American Association of Immunologists
Collection year 2011
Language eng
Subject 1107 Immunology
Formatted 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 {approx}6-fold more IgG2c and generated {approx}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.

Keyword Adaptive immunity
Flow cytometry
Dendritic cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 32 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 35 times in Scopus Article | Citations
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Created: Sun, 07 Mar 2010, 00:03:24 EST