Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis

Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development

Sustainable Design and Business Models in Textile and Fashion Industry

Textile, Clothing and Fashion (TCF) are one of the most unsustainable industries in the world. This challenges triple-bottom line sustainability thus calling for increased intervention by designing sustainable development. Several industrial sustainability models have addressed this issue but they assume incremental improvements and growth while addressing global challenges. Thus a Sustainable Business Model perspective is required to think and go beyond these increments and reconceive radically how businesses should operate to drive system-level sustainability. In line with 8 major sustainable business model archetypes existing, this chapter first contextualizes them in TCF industries, and goes further to identify 5 key design elements (and underlying strategies) underpinning them. The knowledge of these key design elements (product, process, value network, relation, and consumption pattern), upholding a system thinking approach, will further assist both research and practice to strategically develop and improve the sustainable innovations and business models