Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice

Genetic or vitamin D3-induced overexpression of thymic stromal lymphopoietin (TSLP) by keratinocytes results in an atopic dermatitis (AD)-like inflammatory phenotype in mice echoing the discovery of high TSLP expression in epidermis from AD patients. Although skin dendritic cells (DC) are suspected to be involved in AD, direct evidence of a pathogenetic role for skin DC in TSLP-induced skin inflammation has not yet been demonstrated. In a mouse model of AD, i.e. mice treated with the low-calcemic vitamin D3 analogue, MC903, we show that epidermal Langerhans cells (LC)-depleted mice treated with MC903 do neither develop AD-like inflammation nor increased serum IgE as compared to vitamin D3 analogue-treated control mice. Accordingly, we show that, in mice treated with MC903 or in K14-TSLP transgenic mice, expression of maturation markers by LC is increased whereas maturation of dermal DC is not altered. Moreover, only LC are responsible for the polarization of naive CD4+ T cells to a Th2 phenotype, i.e. decrease in interferon-gamma and increase in interleukin (IL)-13 production by CD4+ T cells. This effect of LC on T-lymphocytes does not require OX40-L/CD134 and is mediated by a concomitant down-regulation of IL-12 and CD70. Although it was previously stated that TSLP up-regulates the production of thymus and activation-regulated chemokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) and macrophage-derived chemokine (MDC)/CCL22 by human LC in vitro, our work shows that production of these Th2- cell attracting chemokines is increased only in keratinocytes in response to TSLP overexpression. These results demonstrate that LC are required for the development of AD in mouse models of AD involving epidermal TSLP overexpression.

Politics, Patriotism and Women in Ireland, Britain and Colonial America, c.1700-c.1780

The use of the consumer boycott as a political tool is commonly associated with pre-revolutionary colonial America and has been identified by historians as an important means through which American women were politicized. This article argues that from the late seventeenth century, Irish political discourse advocated the non-consumption of imported goods and support for home manufactures by women in ways that were strikingly similar to those used later in North America. In Ireland and, subsequently in the American colonies, the virtuous woman consumer was given an active public role by political and social commentators. Rather than being a “brilliantly original American invention,” as T. H. Breen has argued, the political exploitation of a consumer boycott and the promotion of local industry were among what Bernard Bailyn has described as the “set of ideas, already in scattered ways familiar” to the revolutionary leaders through the Irish experience. The article also argues that a shared colonial environment gave Irish and American women a public patriotic role in the period, c. 1700–1780 that they did not have in the home countries of England and Scotland.

What Happened to the ‘Development’ in Sustainable Development? Business Guidelines Two Decades After Brundtland

Over twenty years ago ‘Our Common Future’ presented a conceptualization and explanation of the concept of sustainable development. Since then numerous alternative definitions of the concept have been offered, of which at least some are exclusive to each other. At the same time, the role of business in the transition to sustainable development has increasingly received attention. Bringing these two trends in sustainable development together, this paper returns to the Brundtland version of the concept to examine to what extent the original principles of sustainable development are still embedded within key business guidelines, namely the UN Global Compact, the OECD Guidelines for Multinational Enterprises, the ICC Business Charter for Sustainable Development, the CAUX Principles, the Global Sullivan Principles and the CERES Principles. The findings suggest that these business guidelines tend to emphasize environmental rather than social aspects of sustainable development, in particular to the detriment of the original Brundtland prioritization of the needs of the poorest. Furthermore, the attention to environmental aspects stresses win-win situations and has a clear managerialist focus; whereas more conceptual environmental issues concerning systems interdependencies, critical thresholds or systemic limits to growth find little attention. The normative codes and principles targeted at the private sector thus not only add another voice to the multiple discourses on sustainable development but also contribute to a reinterpretation of the original agenda set by Brundtland towards conceptualizations of sustainable development around the needs of industrialised rather than developing countries. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment