CD4+CD25+Foxp3+ regulatory T cells (Tregs) contribute to the maintenance of peripheral tolerance by inhibiting the expansion and function of conventional T cells. Treg development and homeostasis are regulated by the Ag receptor, costimulatory receptors such as CD28 and CTLA-4, and cytokines such as IL-2, IL-10, and TGF-β. Here we show that the proportions of Tregs in the spleen and lymph nodes of mice with inactive p110δ PI3K (p110δD910A/D910A) are reduced despite enhanced Treg selection in the thymus. p110δD910A/D910A CD4+CD25+Foxp3+ Tregs showed attenuated suppressor function in vitro and failed to secrete IL-10. In adoptive transfer experiments, p110δD910A/D910A T cells failed to protect against experimental colitis. The identification of p110δ as an intracellular signaling protein that regulates the activity of CD4+CD25+Foxp3+ Tregs may facilitate the further elucidation of the molecular mechanisms responsible for Treg-mediated suppression.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines. IntroductionAccording to recent estimates by the International Agency for Research on Cancer [1], colorectal cancer (CRC) is the most common cancer in Europe with 432 000 new cases reported annually in men and women combined. It is the second most common cause of cancer deaths in Europe with 212 000 deaths reported in 2008.Worldwide, CRC ranks third in incidence and fourth in mortality with an estimated 1.2 million cases and 0.6 million deaths annually. In the 27 Member States of the European Union (EU), CRC ranks first in incidence and second in mortality, with approximately 334000 new cases and 149000 deaths estimated in 2008.Even in those Member States in the lower range for age-standardized rates of CRC, the burden of disease is significantly greater when compared with many other HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript regions of the world (see reference [1]). CRC is therefore an important health problem across the EU.Screening can be effective in cancer control in populations with a significant burden of CRC, provided the services are of high quality [2]. The aim of CRC screening is to lower the burden of cancer in the population by discovering disease in its early, latent stages [3]. Evidence-based methods permit treatment that is more effective than if disease is diagnosed later when symptoms have occurred. Early treatment of invasive lesions, for example by endoscopic resection of early CRC, can also be less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by avoiding the progression to cancer. Randomized trials in people of average risk invite...

Objective. To investigate the hypothesis that loss of suppression mediated by peripheral CD4؉,CD25؉ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE).

The outermost layer of all immune cells, the glycocalyx, is composed of a complex mixture of glycoproteins, glycolipids and lectins, which specifically recognize particular glycan epitopes. As the glycocalyx is the cell's primary interface with the external environment many biologically significant events can be attributed to glycan recognition. For this reason the rapidly expanding glycomics field is being increasingly recognized as an important component in our quest to better understand the functioning of the immune system. In this review, we highlight the current status of immune cell glycomics, with particular attention being paid to T-and B-lymphocytes and dendritic cells. We also describe the strategies and methodologies used to define immune cell glycomes.

The International Colorectal Cancer Screening Network (ICRCSN) is a global consortium of initiatives delivering organized colorectal cancer (CRC) screening to their populations. The aim of the Network is to promote improvements in quality assurance (QA) and programme evaluation to maximize the benefit and to minimize the risk associated with CRC screening. ICRCSN currently includes 41 member initiatives from 27 countries. The ICRCSN held its second international meeting in Oxford in September 2008 with representatives from 24 countries. This report summarizes the presentations and discussions, the feedback from participants on their current and future needs and the potential role of the ICRCSN in supporting those needs.