Laura Layland

Publications (2)15.77 Total impact

• Source

  Available from: Bianca Schaub

  Article: T regulatory cells in cord blood--FOXP3 demethylation as reliable quantitative marker.

  Jing Liu, Anna Lluis, Sabina Illi, Laura Layland, Sven Olek, Erika von Mutius, Bianca Schaub
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  ABSTRACT: Regulatory T-cells (Tregs), characterized as CD4+CD25(hi) T-cells expressing FOXP3, play a crucial role in controlling healthy immune development during early immune maturation. Recently, FOXP3 demethylation was suggested to be a novel marker for natural Tregs in adults. In cord blood, the role and function of Tregs and its demethylation is poorly understood. We assessed FOXP3 demethylation in cord blood in relation to previously used Treg markers such as CD4+CD25(hi), FOXP3 mRNA, protein expression, and suppressive Treg function. Cord blood mononuclear cells (CBMC) were isolated from 70 healthy neonates, stimulated for 3 days with the microbial stimulus lipid A (LpA), and allergen Dermatophagoides pteronyssinus (Derp1). Tregs (CD4+CD25(hi), intracellular, mRNA FOXP3 expression, isolated cells), DNA methylation of the FOXP3-locus and suppressive Treg function were assessed. Demethylation of FOXP3 in whole blood was specific for isolated CD4+CD25(hi) Tregs. Demethylation of FOXP3 was positively correlated with unstimulated and LpA-stimulated FOXP3 mRNA-expression (p≤0.05), and CD4+CD25(hi) T-cells (p≤0.03). Importantly, increased FOXP3 demethylation correlated with more efficient suppressive capacity of Tregs (r = 0.72, p = 0.005). Furthermore, FOXP3 demethylation was positively correlated with Th2 cytokines (IL-5, IL-13) following LpA-stimulation (p = 0.006/0.04), with Th2 and IL-17 following Derp1+LpA-stimulations (p≤0.009), but not Th1 cytokines (IFN-γ). FOXP3 demethylation reliable quantifies Tregs in cord blood. FOXP3 demethylation corresponds well with the suppressive potential of Tregs. The resulting strict correlation with functionally suppressive Tregs and the relative ease of measurement render it into a valuable novel marker for large field studies assessing Tregs as qualitative marker indicative of functional activity.
  PLoS ONE 01/2010; 5(10):e13267. · 4.09 Impact Factor
• Article: CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo.

  Roland Rad, Lena Brenner, Stefan Bauer, Susanne Schwendy, Laura Layland, Clarissa Prazeres da Costa, Wolfgang Reindl, Anar Dossumbekova, Mathias Friedrich, Dieter Saur, Hermann Wagner, Roland M Schmid, Christian Prinz
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  ABSTRACT: Helicobacter pylori infects more than half of the world's population. In contrast to most other pathogens, the microbe persists for the virtual life of its host. It is unclear why the immune system is unable to eliminate the infection, but recent studies suggested that CD4+/CD25+/Foxp3+ regulatory T cells may be involved in this process. By using a mouse model of infection and gastric biopsies from 108 patients, we performed a detailed descriptive and functional characterization of the Helicobacter-induced CD25+/Foxp3+ T-cell response. In C57BL/6 mice, H pylori induced a marked gastric Foxp3+ T-cell response, which increased over several months together with the severity of inflammation, until a stable homeostatic situation became established. Accordingly, in Helicobacter-infected patients, but not in uninfected individuals, large numbers of gastric Foxp3+ T cells were detected immunohistochemically. To define the functional in vivo relevance of this response, CD25+ cells were depleted systemically in mice by using an anti-CD25 monoclonal antibody (PC61). Already 4 weeks after infection, PC61-treated mice, but not untreated animals, developed a severe gastritis with heightened cytokine expression and increased numbers of mucosal T cells, B cells, and macrophages. This was accompanied by increased titers of H pylori-specific IgG1 and IgG2c antibodies in the sera of PC61-treated mice. This increased gastric inflammatory response in CD25-depleted mice was associated with reduced bacterial loads. CD25+/Foxp3+ T cells actively participate in the immune response to H pylori. In vivo depletion of these cells in infected mice leads to increased gastric inflammation and reduced bacterial colonization.
  Gastroenterology 09/2006; 131(2):525-37. · 11.68 Impact Factor