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Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host's clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm's initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours. SAg-triggered human IL-17A production was characterized by remarkably high mRNA stability for this cytokine. A distinct subpopulation of CD4 effector memory T (T) cells that secrete IL-17A, but not IFN-γ, was responsible for early IL-17A production. We found mouse "T-17" cells to be enriched within the intestinal epithelium and among lamina propria lymphocytes. Furthermore, interfering with IL-17A receptor signaling in human PBMCs attenuated the expression of numerous inflammatory mediators implicated in the TSS-associated cytokine storm. IL-17A receptor blockade also abrogated the secondary effect of SAg-stimulated PBMCs on human dermal fibroblasts as judged by C/EBP δ expression. Finally, the early IL-17A response to SAgs was pathogenic because in vivo neutralization of IL-17A in humanized mice ameliorated hepatic and intestinal damage and reduced mortality. Together, our findings identify CD4 T cells as a key effector of TSS and reveal a novel role for IL-17A in TSS immunopathogenesis. Our work thus elucidates a pathogenic, as opposed to protective, role for IL-17A during Gram-positive bacterial infections. Accordingly, the IL-17-IL-17R axis may provide an attractive target for the management of SAg-mediated illnesses.

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The effect of the patternmaker’s proficiency on the creation of clothing was investigated by the observation of the patternmaking process for clothing that satisfies the designer. We asked Japanese and French patternmakers to make a clothing pattern for the same design. The reasons for the differences in resultant clothing patterns and toiles made by the two patternmakers are discussed. Although the patternmaking processes used by the proficient patternmakers were similar, the resultant patterns were different owing to different recognition of the design. In particular, the shape and size of the collar that the designer emphasized in the illustration were different in the resultant patterns. Differences in patternmaking originated from differences in the patternmakers′ levels of expertise in terms of education, experience, and proficiency. However, the designer was satisfied with both patterns.