title: SerpinB2 is critical to Th2 immunity against enteric nematode infection.
abstract: SerpinB2, a member of the serine protease inhibitor family, is expressed by macrophages and is significantly upregulated by inflammation. Recent studies implicated a role for SerpinB2 in the control of Th1 and Th2 immune responses, but the mechanisms of these effects are unknown. In this study, we used mice deficient in SerpinB2 (SerpinB2(-/-)) to investigate its role in the host response to the enteric nematode, Heligmosomoides bakeri. Nematode infection induced a STAT6-dependent increase in intestinal SerpinB2 expression. The H. bakeri-induced upregulation of IL-4 and IL-13 expression was attenuated in SerpinB2(-/-) mice coincident with an impaired worm clearance. In addition, lack of SerpinB2 in mice resulted in a loss of the H. bakeri-induced smooth muscle hypercontractility and a significant delay in infection-induced increase in mucosal permeability. Th2 immunity is generally linked to a CCL2-mediated increase in the infiltration of macrophages that develop into the alternatively activated phenotype (M2). In H. bakeri-infected SerpinB2(-/-) mice, there was an impaired infiltration and alternative activation of macrophages accompanied by a decrease in the intestinal CCL2 expression. Studies in macrophages isolated from SerpinB2(-/-) mice showed a reduced CCL2 expression, but normal M2 development, in response to stimulation of Th2 cytokines. These data demonstrate that the immune regulation of SerpinB2 expression plays a critical role in the development of Th2-mediated protective immunity against nematode infection by a mechanism involving CCL2 production and macrophage infiltration.
authors: Department of Medicine, Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Aiping
authors: A
authors: Zhao
authors: Zhonghan
authors: Z
authors: Yang
authors: Rex
authors: R
authors: Sun
authors: Viktoryia
authors: V
authors: Grinchuk
authors: Sarah
authors: S
authors: Netzel-Arnett
authors: Ian E
authors: IE
authors: Anglin
authors: Kathryn Hodge
authors: KH
authors: Driesbaugh
authors: Luigi
authors: L
authors: Notari
authors: Jennifer A
authors: JA
authors: Bohl
authors: Kathleen B
authors: KB
authors: Madden
authors: Joseph F
authors: JF
authors: Urban
authors: Toni M
authors: TM
authors: Antalis
authors: Terez
authors: T
authors: Shea-Donohue
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D007422:Intestines / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism / Q000469:parasitology; D009349:Nematode Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D017396:Plasminogen Activator Inhibitor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017396:Plasminogen Activator Inhibitor 2
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