Search

Institutional and individual stigmatization represent major barriers that prevent children with disabilities from accessing education. It can be presumed that children with disabilities are labeled as such even in inclusive educational settings and that teachers' attitudes toward inclusive education and children with disabilities play a crucial role in this context. Against this background, the present study aims to (a) apply and conceptualize the mixed-blessings model in the context of stigma-related reactions to children's disability labels in inclusive education and (b) shed light on the causal attributions of teachers that underlie stigma-related attitudes toward children with various disabilities. A 3 × 2 × 2 × 2 × 2 online experiment examined the ways in which disability-specific causes and symptoms, the type of disability in question, the children's sex, and efficacy cues regarding educational efforts affect future teachers' attitudes toward and expectations of inclusive education as well as their social distance toward children with disabilities. The participants in this experiment were N  = 605 German student and trainee teachers representing different types of teaching professions. A multivariate analysis of variance (MANOVA) revealed that, in particular, the cause attributed to the disability, the depicted type of disability and the probability of learning success led to changes in attitudes. Respondents' teaching self-efficacy and their status as students or trainees emerged as moderators of the effect of pupils' type of disability. As a result, teacher education and training as well as communication regarding pupils with disabilities require a high degree of sensitivity to disability-specific and efficacy-related cues to prevent (accidental) professional or institutional stigmatization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Röhm, Grengel, Möhring, Zensen-Möhring, Nellen and Hastall.)

Background: Forkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive T cells into Tregs that can downregulate the effector function of other T cells. We previously detected the expression of FoxP3 in retinal pigment epithelial (RPE) cells, forming the outer blood-retina barrier of the immune privileged eye., Methods: We investigated the expression, subcellular localization, and phosphorylation of FoxP3 in RPE cells in vivo and in vitro after treatment with various stressors including age, retinal laser burn, autoimmune inflammation, exposure to cigarette smoke, in addition of IL-1β and mechanical cell monolayer destruction. Eye tissue from humans, mouse models of retinal degeneration and rats, and ARPE-19, a human RPE cell line for in vitro experiments, underwent immunohistochemical, immunofluorescence staining, and PCR or immunoblot analysis to determine the intracellular localization and phosphorylation of FoxP3. Cytokine expression of stressed cultured RPE cells was investigated by multiplex bead analysis. Depletion of the FoxP3 gene was performed with CRISPR/Cas9 editing., Results: RPE in vivo displayed increased nuclear FoxP3-expression with increases in age and inflammation, long-term exposure of mice to cigarette smoke, or after laser burn injury. The human RPE cell line ARPE-19 constitutively expressed nuclear FoxP3 under non-confluent culture conditions, representing a regulatory phenotype under chronic stress. Confluently grown cells expressed cytosolic FoxP3 that was translocated to the nucleus after treatment with IL-1β to imitate activated macrophages or after mechanical destruction of the monolayer. Moreover, with depletion of FoxP3, but not of a control gene, by CRISPR/Cas9 gene editing decreased stress resistance of RPE cells., Conclusion: Our data suggest that FoxP3 is upregulated by age and under cellular stress and might be important for RPE function., (© 2022. The Author(s).)

Objectives: AAV vectors are widely used in gene therapy, but the prevalence of neutralizing antibodies raised against AAV serotypes in the course of a natural infection, as well as innate and adaptive immune responses induced upon vector administration, is still considered an important limitation. In ocular gene therapy, vectors applied subretinally bear the risk of retinal detachment or vascular leakage. Therefore, new AAV vectors that are suitable for intravitreal administration for photoreceptor transduction were developed., Methods: Here, we compared human immune responses from donors with suspected previous AAV2 infections to the new vectors AAV2.GL and AAV2.NN-two capsid peptide display variants with an enhanced tropism for photoreceptors-with the parental serotype AAV2 (AAV2 WT). We investigated total and neutralizing antibodies, adaptive and innate cellular immunogenicity determined by immunofluorescence staining and flow cytometry, and cytokine secretion analyzed with multiplex beads., Results: While we did not observe obvious differences in overall antibody binding, variants-particularly AAV2.GL-were less sensitive to neutralizing antibodies than the AAV2 WT. The novel variants did not differ from AAV2 WT in cellular immune responses and cytokine production in vitro., Conclusion: Due to their enhanced retinal tropism, which allows for dose reduction, the new vector variants are likely to be less immunogenic for gene therapy than the parental AAV2 vector.