Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis.

BACKGROUND: Activation of innate pattern-recognition receptors promotes CD4+ T-cell-mediated autoimmune myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms that counterregulate exaggerated heart-specific autoimmunity are poorly understood. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with α-myosin heavy chain peptide and complete Freund's adjuvant. Together with interferon-γ, heat-killed Mycobacterium tuberculosis, an essential component of complete Freund's adjuvant, converted CD11b(hi)CD11c(-) monocytes into tumor necrosis factor-α- and nitric oxide synthase 2-producing dendritic cells (TipDCs). Heat-killed M. tuberculosis stimulated production of nitric oxide synthase 2 via Toll-like receptor 2-mediated nuclear factor-κB activation. TipDCs limited antigen-specific T-cell expansion through nitric oxide synthase 2-dependent nitric oxide production. Moreover, they promoted nitric oxide synthase 2 production in hematopoietic and stromal cells in a paracrine manner. Consequently, nitric oxide synthase 2 production by both radiosensitive hematopoietic and radioresistant stromal cells prevented exacerbation of autoimmune myocarditis in vivo. CONCLUSIONS: Innate Toll-like receptor 2 stimulation promotes formation of regulatory TipDCs, which confine autoreactive T-cell responses in experimental autoimmune myocarditis via nitric oxide. Therefore, activation of innate pattern-recognition receptors is critical not only for disease induction but also for counterregulatory mechanisms, protecting the heart from exaggerated autoimmunity.

Valuing People, Valuing Their Participation - A Strategy for Personal and Public Involvement for the Public Health Agency and Health and Social Care Board

Personal and Public Involvement (PPI) is about involving those who use Health and Social Care (HSC) services, or care for those who use services, with those who plan and deliver services. This involvement can sometimes relate to individuals (personal), or groups, or the wider community (public).This Strategy shows the direction that both the PHA and the HSCB are committed to, in their development of PPI.

Public Health Agency Business plan 2012-2013

This Business Plan sets out the key priorities and actions that will be progressed by the Public Health Agency (PHA) in 2012/13. The PHA believes that these actions will have the biggest impact on improving levels of health and social wellbeing, protecting the health of the community, and ensuring patients continue to receive high quality and safe treatment and care services.The business plan is available to download below.

Public Health Agency Business plan 2013-2014

This Business Plan sets out the key priorities and actions that will be progressed by the Public Health Agency (PHA) in 2013/14. The PHA believes that these actions will have the biggest impact on improving levels of health and social wellbeing, protecting the health of the community, and ensuring patients continue to receive high quality and safe treatment and care services.The business plan is available to download below.

Public Health Agency Business plan 2014-2015

This Business Plan sets out the key priorities and actions that will be progressed by the Public Health Agency (PHA) in 2014/15. The PHA believes that these actions will have the biggest impact on improving levels of health and social wellbeing, protecting the health of the community, and ensuring patients continue to receive high quality and safe treatment and care services.The business plan is available to download below.

Lifeline Consultation Report - A summary of the feedback to the Public Health Agency's public consultation process on the Lifeline Crisis Response Service

This report is a summary of the feedback from the public consultation process on the current Lifeline contract and future options.

Joint Commissioning Plan of the Health and Social Care Board and the Public Health Agency: 2010-2011

Legislation enacted on 1 April 2009 created a new Commissioning system with the establishment of a region-wide Health and Social Care Board, including 5 Local Commissioning Groups (LCGs), and a Public Health Agency. In line with Departmental direction and guidance the objectives of the new commissioning arrangementswere to:- Approach the future delivery of Health and Social Care from a region-wide perspective focused on outcomes.- Ensure local sensitivity through the creation of five Local Commissioning Groups reflective of their areas.

Public Health Agency Business plan 2010-2011

This second corporate business plan explains the purpose of the PHA and focuses on health improvement, health protection and addressing health inequalities. The business plan is available to download below.

Public Health Agency Annual Business Plan 2015-2016

This Business Plan sets out the key priorities and actions that will be progressed by the Public Health Agency (PHA) in 2015/16. The PHA believes that these actions will have the biggest impact on improving levels of health and social wellbeing, protecting the health of the community, and ensuring patients continue to receive high quality and safe treatment and care services.The business plan is available to download below.

Public Health Agency Self- Harm Symposium Conference Report

Public Health Agency Self- Harm Symposium 27 February 2015, Conference Report.

Regulatory assessment of in vitro skin corrosion and irritation data within the European framework: Workshop recommendations

Validated in vitro methods for skin corrosion and irritation were adopted by the OECD and by the European Union during the last decade. In the EU, Switzerland and countries adopting the EU legislation, these assays may allow the full replacement of animal testing for identifying and classifying compounds as skin corrosives, skin irritants, and non irritants. In order to develop harmonised recommendations on the use of in vitro data for regulatory assessment purposes within the European framework, a workshop was organized by the Swiss Federal Office of Public Health together with ECVAM and the BfR. It comprised stakeholders from various European countries involved in the process from in vitro testing to the regulatory assessment of in vitro data. Discussions addressed the following questions: (1) the information requirements considered useful for regulatory assessment; (2) the applicability of in vitro skin corrosion data to assign the corrosive subcategories as implemented by the EU Classification, Labelling and Packaging Regulation; (3) the applicability of testing strategies for determining skin corrosion and irritation hazards; and (4) the applicability of the adopted in vitro assays to test mixtures, preparations and dilutions. Overall, a number of agreements and recommendations were achieved in order to clarify and facilitate the assessment and use of in vitro data from regulatory accepted methods, and ultimately help regulators and scientists facing with the new in vitro approaches to evaluate skin irritation and corrosion hazards and risks without animal data.

Plasmacytoid dendritic cells and regulatory T cells in the tumor microenvironment: A dangerous liaison.

Tumor-infiltrating plasmacytoid dendritic cells (pDCs) have been associated with poor patient prognosis. We have recently uncovered the ability of pDCs to activate and expand a subset of tumor-infiltrating FOXP3(+) regulatory T cells that express inducible costimulator (ICOS), providing new insights into the mechanisms that govern the escape of cancer from immunosurveillance.

The Institutional Foundations of Regulatory Capitalism: The Diffusion of Independent Regulatory Agencies in Western Europe

This article studies the diffusion of the main institutional feature of regulatory capitalism, namely, independent regulatory agencies. While only a few such authorities existed in Europe in the early 1980s, by the end of the twentieth century they had spread impressively across countries and sectors. The analysis finds that three classes of factors (bottom-up, top-down, and horizontal) explain this trend. First, the establishment of independent regulatory agencies was an attempt to improve credible commitment capacity when liberalizing and privatizing utilities and to alleviate the political uncertainty problem, namely, the risk to a government that its policies will be changed when it loses power. Second, Europeanization favored the creation of independent regulators. Third, individual decisions were interdependent, as governments were influenced by the decisions of others in an emulation process where the symbolic properties of independent regulators mattered more than the functions they performed.

The Formal Independence of Regulators: A Comparison of 17 Countries and 7 Sectors

This article seeks to explain the pattern of delegation to independent regulatory agencies in Western Europe. Two types of arguments are advanced to explain variations in the formal independence of regulators. Firstly, the need for governments to increase their credible commitment capacity may lead them to delegate regulation to an agency that is partly beyond their direct control. Secondly, delegation may be a response to the political uncertainty problem, which arises when governments are afraid of being replaced by another coalition with different preferences, which could decide to change existing policy choices. In addition, veto players may constitute a functional equivalent of delegation, since they influence policy stability and therefore tend to mitigate both the credibility and the political uncertainty problems. These arguments are consistent with the results of the empirical analysis of the formal independence of regulators in seventeen countries and seven sectors.