| First Author | Zhao A | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 11 | Pages | 5779-87 |
| PubMed ID | 23630350 | Mgi Jnum | J:204777 |
| Mgi Id | MGI:5543343 | Doi | 10.4049/jimmunol.1200293 |
| Citation | Zhao A, et al. (2013) SerpinB2 is critical to Th2 immunity against enteric nematode infection. J Immunol 190(11):5779-87 |
| abstractText | 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. |
