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Chen J.,Fudan University | Chen J.,National Health Research Institute | Xie L.,National Health Research Institute | Xie L.,Osaka University | And 5 more authors.
International Immunopharmacology | Year: 2011

Regulatory T (Treg) cells play an important role in the pathogenesis of inflammatory bowel disease (IBD). In the present study, we found that a superagonistic CD28-specific monoclonal antibody (supCD28mAb, D665) could preferentially stimulate expansion of CD4+Foxp3+ Treg cells. Foxp3 EGFP mice were orally administrated with 3.5% DSS for 5 days, and intraperitoneally injected supCD28mAb 1 mg/mice in treated group. All of the mice were sacrificed on day 8, and both clinical and histological parameters showed that the severity of colitis was significantly reduced in treated group compared to controls. In treated group, the proportion of CD103, CD152 and CD62L expression on Foxp3+Treg cells in the spleen and mesenteric lymph node were higher than controls. Furthermore, qRT-PCR analysis showed that expression of anti-inflammatory cytokines such as IL-10, TGF-β was significantly increased in treated group. Taken together, our data demonstrated that supCD28mAb targets CD4+Foxp3+Treg cells expansion in vivo, maintains and enhances their regulatory functions, to reduce the damage of colon in dextran sulfate sodium (DSS)-induced mouse colitis by secreting a large amount of IL-10. It represents a major advance towards the therapeutic use of polyclonally activated Treg cells as cellular therapy for treatment of IBD. © 2010 Elsevier B.V.


Kitazawa Y.,National Health Research Institute | Kitazawa Y.,Osaka University | Li X.-K.,National Health Research Institute | Liu Z.,National Health Research Institute | And 4 more authors.
Cell Transplantation | Year: 2010

Naturally occurring CD4+CD25+ Treg cells (nTregs) can be exploited to establish an immunologic tolerance to non-self-antigens. The in vivo administration of a single superagonistic CD28-specific monoclonal antibody (supCD28mAb) to naive rat preferentially expanded the nTregs, which induced a potent inhibition of lethality of the graft-versus-host (GvH) diseases. The appearance of increased Foxp3 molecules was accompanied with a polarization towards a Th2 cytokine profile with a decreased production of IFN-γ and increased production of IL-4 and IL-10 in the serum of the antibody-treated rat. The peripheral Foxp3 nTregs are decreased in acute GvHD, while supCD28mAb administration showed that nTregs were preferentially proliferating in vivo, thus resulting in the significant prevention of the GvH disease. Furthermore, antigen-specific nTregs could suppress conventional T-cell proliferation stimulated with alloantigen in vitro. Taken together, our findings demonstrate that the potent regulatory functions of the Tregs for the treatment of GvHD are antigen specific. These data also provide evidence that GvHD is associated with decrease of Tregs in the periphery of the host. The determination of the Foxp3 Tregs can be a helpful tool to discriminate GvHD severity and lethality after allogeneic stem cell transplantation. Copyright © 2010 Cognizant Comm. Corp.


Alsheimer M.,University of Wuurzburg | Jahn D.,University of Wuurzburg | Schramm S.,University of Wuurzburg | Benavente R.,University of Wuurzburg
Epigenetics and Human Health | Year: 2011

Nuclear lamins are important structural protein components of the nuclear envelope. The composition and properties of the nuclear lamina of spermatogenic cells differ significantly from those of somatic cells of the same species. Mammalian spermatogenic cells selectively express short lamin isoforms showing several peculiarities. In this chapter, we summarize what is known about germ linespecific lamins and discuss their possible relevance for germ cell differentiation and fertility. © Springer-Verlag Berlin Heidelberg 2011.


Bibova I.,Academy of Sciences of the Czech Republic | Hot D.,Applied Genomics | Keidel K.,Academy of Sciences of the Czech Republic | Amman F.,The Interdisciplinary Center | And 4 more authors.
RNA Biology | Year: 2015

Bordetella pertussis, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen B. pertussis under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in B. pertussis. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in B. pertussis cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the hfq mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the B. pertussis T3SS. Likewise, expression of virulence factors vag8 and tcfA encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the hfq mutant. Importantly, for the first time we demonstrate that B. pertussis T3SS can be activated upon contact with macrophage cells in vitro. © Ilona Bibova, David Hot, Kristina Keidel, Fabian Amman, Stephanie Slupek, Ondrej Cerny, Roy Gross, and Branislav Vecerek.

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