Clappgoodwin4159

Ribeiro, Fattori, Silva, Prazeres, Queiroz-Junior, Santana, Costa, Beltrami, Costa, Birbrair, Verri, Lopes, Cunha, Teixeira, Amaral and Pinho.Pemphigus is a chronic autoimmune blistering disorder, characterized by (muco-)cutaneous erosions due to autoantibodies against desmoglein 3 and/or 1. Pemphigus induction might be associated with drugs, malignancy or radiation therapy (RT); the latter being only rarely described. A rigorous literature review revealed around 30 cases of RT-associated pemphigus, which had been primarily treated with topical and/or systemic steroids, in some cases also dapsone or few other immunosuppressive agents were given. The most common underlying cancer type was breast cancer. We here present a 63-year-old male patient, who was pre-treated with adjuvant RT for larynx carcinoma 3 months before admission. He developed extensive cutaneous, ocular, and oral erosions. Despite the clinical picture comparable to a paraneoplastic pemphigus, the diagnosis of pemphigus vulgaris of mucocutaneous type was established based on the direct immunofluorescence, showing positive cell surface IgG and discrete C3 deposits, with matching cell surface IgG pattern on monkey esophagus. Serum autoantibodies to desmoglein 1 and 3 were highly positive. No further autoantibodies were found, thus paraneoplastic pemphigus was excluded. Cell Cycle inhibitor The patient was treated with high dose prednisolone, partially given intravenously up to 2 mg/kg per day, as well as topical disinfectants and class IV steroid cream. To stabilize the disease rituximab 2 × 1,000 mg was given, leading to clinical and serological remission for up to 2 years now. We show that rituximab represents a good treatment option for the frequently treatment-refractory RT-associated pemphigus, a clinically and immunologically specific RT-induced skin disorder, resulting in long-term clinical, and serological remission. Copyright © 2020 Schauer, Ishii, Mockenhaupt, Bruckner-Tuderman, Hashimoto and Kiritsi.Group 2 innate lymphoid cells (ILC2s) are enriched at mucosal sites, including the lung, and play a central role in type 2 immunity and maintaining tissue homeostasis. As a result, since their discovery in 2010, research into ILC2s has increased markedly. Numerous strategies have been used to define ILC2s by flow cytometry, often utilizing different combinations of surface markers despite their expression being variable and context-dependent. In this study, we sought to generate a comprehensive characterization of pulmonary ILC2s, identifying stable and context specific markers from different pulmonary compartments following different airway exposures in different strains of mice. Our analysis revealed that pulmonary ILC2 surface marker phenotype is heterogeneous and is influenced by mouse strain, pulmonary location, in vivo treatment/exposure and ex vivo stimulation. Therefore, we propose that a lineage negative cell expressing CD45 and Gata3 defines an ILC2, and subsequent surface marker expression should be used to describe their phenotype in context-specific scenarios. Copyright © 2020 Entwistle, Gregory, Oliver, Branchett, Puttur and Lloyd.Pre-existing immunity to AAV capsid may compromise the safety and efficiency of rAAV-mediated gene transfer in patients. Anti-capsid cytotoxic immune responses have proven to be a challenge to characterize because of the scarcity of circulating AAV-specific CD8+ T lymphocytes which can seldom be detected with conventional flow cytometry or ELISpot assays. Here, we used fluorescent MHC class I tetramers combined with magnetic enrichment to detect and phenotype AAV8-specific CD8+ T cells in human PBMCs without prior amplification. We showed that all healthy individuals tested carried a pool of AAV8-specific CD8+ T cells with a CD45RA+ CCR7- terminally-differentiated effector memory cell (TEMRA) fraction. Ex vivo frequencies of total AAV-specific CD8+ T cells were not predictive of IFNγ ELISpot responses but interestingly we evidenced a correlation between the proportion of TEMRA cells and IFNγ ELISpot positive responses. TEMRA cells may then play a role in recombinant AAV-mediated cytotoxicity in patients with preexisting immunity. Overall, our results encourage the development of new methods combining increased detection sensitivity of AAV-specific T cells and their poly-functional assessment to better characterize and monitor AAV capsid-specific cellular immune responses in the perspective of rAAV-mediated clinical trials. Copyright © 2020 Vandamme, Xicluna, Hesnard, Devaux, Jaulin, Guilbaud, Le Duff, Couzinié, Moullier, Saulquin and Adjali.Interleukin-2 (IL-2) inducible T-cell kinase (ITK) is a non-receptor tyrosine kinase highly expressed in T-cell lineages and regulates multiple aspects of T-cell development and function, mainly through its function downstream of the T-cell receptor. Itk deficiency can lead to CD4 lymphopenia and Epstein-Bar virus (EBV)-associated lymphoproliferation and recurrent pulmonary infections in humans. However, the role of the ITK signaling pathway in pulmonary responses in active tuberculosis due to Mtb infection is not known. We show here that human lungs with active tuberculosis exhibit altered T-cell receptor/ITK signaling and that Itk deficiency impaired early protection against Mtb in mice, accompanied by defective development of IL-17A-producing γδ T cells in the lungs. These findings have important implications of human genetics associated with susceptibility to Mtb due to altered immune responses and molecular signals modulating host immunity that controls Mtb activity. Enhancing ITK signaling pathways may be an alternative strategy to target Mtb infection, especially in cases with highly virulent strains in which IL-17A plays an essential protective role. Copyright © 2020 Huang, Ye, McGee, Nidetz, Elmore, Limper, Southard, Russell, August and Huang.Understanding of pathogenesis and protection mechanisms underlying influenza-Streptococcus pneumoniae co-infection may provide potential strategies for decreasing its high morbidity and mortality. Interleukin-6 (IL-6) is an important cytokine that acts to limit infection-related inflammation; however, its role in co-infected pneumonia remains unclear. Here we show that the clinically relevant co-infected mice displayed dramatically elevated IL-6 levels; which was also observed in patients with co-infected pneumonia. IL-6 -/- mice presented with increased bacterial burden, early dissemination of bacteria to extrapulmonary sites accompanied by aggravated pulmonary lesions and high mortality when co-infection. This protective function of IL-6 is associated with cellular death and macrophage function. Importantly, therapeutic administration of recombinant IL-6 protein reduced cells death in BALF, and enhanced macrophage phagocytosis through increased MARCO expression. This protective immune mechanism furthers our understanding of the potential impact of immune components during infection and provides potential therapeutic avenues for influenza-Streptococcus pneumoniae co-infected pneumonia.