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The expression profile of the ubiquitin-like modifier FAT10 in immune cells suggests cell type-specific functions

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Abstract

The TNF and IFN-γ-inducible ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) is most prominently expressed in immunological tissues but information regarding basal expression and inducibility of FAT10 in the different types of immune cells is still lacking. Hence, we investigated FAT10 mRNA expression in the major human and murine immune cell subsets, and FAT10 protein expression in human leukocytes. We isolated the different human leukocytes from peripheral blood and the murine immune cell subsets from spleen. The purified leukocytes were left untreated or stimulated with TNF and INF-γ or LPS to induce FAT10 followed by quantitative real-time PCR or western blot analysis. Basal expression of FAT10 mRNA and protein was generally low but strongly up-regulated by IFN-γ and TNF in all immune cell subsets. LPS treatment induced FAT10 expression marginally in human CD8+ T cells and murine granulocytes, but it increased Fat10 expression significantly in murine regulatory T cells. Yet, in human CD8+ T cells, natural killer cells, natural killer T cells, and dendritic cells, the FAT10 mRNA was expressed without induction. Similarly, murine macrophages, monocytes, and regulatory T cells expressed Fat10 in the absence of stimulation. In summary, our findings suggest particular functions of FAT10 in these cell types. Furthermore, we observed not only a cell type-specific but also a species-specific basal FAT10 expression profile. Our data will serve as a guideline for future investigations to further elucidate FAT10’s role in the immune system.

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Acknowledgements

We acknowledge Annette Sommershof and Wendy Bergmann from the flow cytometry centre FlowKon for expert support during flow cytometry and cell sorting, Hans Christian Probst for providing Treg reporter mice, and Allon Canaan and Sherman Weissman for the contribution of FAT10-/- mice.

Funding

This study was funded by the German Research Foundation (DFG) Collaborative Research Center SFB969, project C01 (to M. G.) and grant Nr. BA 4199/2-1 to M.B. and GR 1517/2.4 and GR 1517/10-2 to M.G. and SwissLife Jubiläumsstiftung to MB.

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Correspondence to Marcus Groettrup.

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The authors declare that they have no conflict of interest.

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All applicable international and national guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution.

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Schregle, R., Mah, M.M., Mueller, S. et al. The expression profile of the ubiquitin-like modifier FAT10 in immune cells suggests cell type-specific functions. Immunogenetics 70, 429–438 (2018). https://doi.org/10.1007/s00251-018-1055-5

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  • DOI: https://doi.org/10.1007/s00251-018-1055-5

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