Dendritic cells (DC) are central to regulating innate and adaptive immune responses. Strategies that modify DC function provide new therapeutic opportunities in autoimmune diseases and transplantation. Current pharmacological approaches can alter DC phenotype to induce tolerogenic DC (tolDC), a maturation-resistant DC subset capable of directing a regulatory immune response that are being explored in current clinical trials. The classical phenotypic characterization of tolDC is limited to cell-surface marker expression and anti-inflammatory cytokine production, although these are not specific. TolDC may be better defined using gene signatures, but there is no consensus definition regarding genotypic markers. We address this shortcoming by analyzing available transcriptomic data to yield an independent set of differentially expressed genes that characterize human tolDC. We validate this transcriptomic signature and also explore gene differences according to the method of tolDC generation. As well as establishing a novel characterization of tolDC, we interrogated its translational utility in vivo, demonstrating this geneset was enriched in the liver, a known tolerogenic organ. Our gene signature will potentially provide greater understanding regarding transcriptional regulators of tolerance and allow researchers to standardize identification of tolDC used for cellular therapy in clinical trials.

Basic science research remains fundamental to progress in clinical care, understanding of disease pathophysiology and underpinning the evolution of personalised medicine. Exposure to research is pivotal to educating students, but a declining profile of basic science research has the potential to erode research capacity further. The capacity for women to engage in research and remain in academia long term is continually challenged by negative gender-based experiences and institutional barriers. The authors explored themes and authorship of abstracts presented at Australia and New Zealand--based nephrology conferences, as a surrogate marker of trends in research activity and gender engagement. Basic science research and female senior authorship declined during the study period, which has serious implications for the future of nephrology.

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