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- W3014836164 abstract "<h3>Purpose</h3> Dendritic cells (DC) are central to the induction and maintenance of T regulatory cells (T-regs) and lung allograft tolerance. We previously identified tumor necrosis factor 2 positive DC (TNFR2<sup>+</sup>DC) as a subset of lung resident DC responsible for antigen-specific Th2 mediated response and inflammation in mice model of asthma. Interestingly, TNFR2<sup>+</sup>DC is plastic and intranasal administration of IFNβ reprograms TNFR2<sup>+</sup>DC to generate regulatory T-cells and reverses lung inflammation in mice. We set out to characterize TNFR2<sup>+</sup>DC and the response to IFNβ in healthy human donor and CLAD lungs. <h3>Methods</h3> We evaluated single-cell suspensions from the unused healthy human donor lungs from the lobar transplantation, and CLAD explant lung tissue from patients undergoing re-transplantation. Identification of TNFR2<sup>+</sup>DC populations and the response to IFNβ (200ng IFNβ, R&D systems INC. MN, USA) were investigated with flow cytometry analysis. <h3>Results</h3> We successfully identified the TNFR2<sup>+</sup>DC population in healthy donor and CLAD lung tissues (n=4/group) (Figure 1A). The healthy lung TNFR2<sup>+</sup>DC constitutively express TGFβ1, IDO-1, and Arg-1, which has a similar phenotype to tolerogenic DC in mouse lungs. Conversely, TNFR2<sup>+</sup>DC from CLAD patients had decreased TGFβ1, Arg-1, PD-L1, but increased IL-4 and IL-23 expression (Figure 1B). Treatment with IFNβ increased TGFβ1, Arg1, and decreased IL-4 expression in CLAD TNFR2<sup>+</sup>DC. Thus, similar to mice, treatment with IFNβ reprograms pathogenic TNFR2<sup>+</sup>DC in CLAD to phenotypically tolerogenic DC (Figure 1C). <h3>Conclusion</h3> We identified TNFR2<sup>+</sup>DC in healthy human donor lung and CLAD. Healthy human donor lung has a phenotypically tolerogenic TNFR2<sup>+</sup>DC. Conversely, TNFR2<sup>+</sup>DC in CLAD shows inflammatory markers, and treatment with IFNβ reprograms pathogenic DC to a tolerogenic phenotype. Further studies are required to assess the utility of TNFR2<sup>+</sup>DC plasticity for achieving lung allograft tolerance." @default.
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- W3014836164 date "2021-04-01" @default.
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- W3014836164 title "Interferon-beta (IFNb) Reprograms Pathogenic Lung Dendritic Cells in Human Chronic Lung Allograft Dysfunction (CLAD)" @default.
- W3014836164 doi "https://doi.org/10.1016/j.healun.2021.01.1882" @default.
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