Invariant Natural Killer T (iNKT) Cells Prevent Autoimmunity, but Induce Pulmonary Inflammation in Cystic Fibrosis

Background/Aims: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. Methods: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. Results: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17+ iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. Conclusion: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation

Bestial metamorphoses: Blake’s variations on trans-human change in Dante’s Hell

William Blake’s engagement with Dante Alighieri’s Divine Comedy (1824-7) illuminates the convergence of Classical and Christian iconography at the heart of Blake’s bestiary. Oswald Spengler coined the term ‘pseudomorphosis’ to ‘denote the unwilling conformity of a new and dynamic culture to the forms and formulas of an older culture’. Erwin Panofsky took up the concept to investigate divergences in form and content between text and image in the medieval translation of classical literature and visual culture. Against Spengler’s dramatic take on the fight towards form, and Panofsky’s recuperation of medium divergence in cultural translation, Theodor W. Adorno read pseudomorphosis as a medium’s imitation of another medium, an uncritical ‘stage in the process of convergence’. Drawing on the iconological school’s analysis of the pseudomorphic articulations of cultural transmission, I wish to explore Blake’s monsters as Christian reinventions of classical mythology. Dante’s emblematic bestiary reinvents monsters from classical literature in a series of transgressions of the boundaries of species. This essay will draw on the debated concept of pseudomorphosis to explore the dialectic tension between assimilation, parody, and disintegration of form in Blake’s reinvention of Dante’s visions of hell. Classical sculptures used as prototypes of the human ideal are subjected to a series of demonic inversions. Hybrid forms and transformations culminate in the reversible serpent metamorphoses that express the bestial condition of the thieves in Cantos XXIV and XXV of Inferno. The multiplication of images Blake devotes to this case of transhuman change indicates its key place in the interminglings between man and beast in his approach to the Commedia. This chapter explores Blake’s serpent sequence and the possibilities of metamorphosis as a way of interrogating alternative models of animal human encounter. The frame of punishment suggests that Dante’s bestial metamorphoses represent a series of transgressions of boundaries. However, Blake’s versions bring to light alternative possibilities in the handling of species, showing coexistence or overlaps, intermediate steps in a continuum, fusion through commingling. Metamorphosis itself changes with acts of translation – between languages, genres, and media