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The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8<sup>+</sup> T cells

The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8+ T cells

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MAH, Mei Min, Michael BASLER, Marcus GROETTRUP, 2019. The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8+ T cells. In: Molecular Immunology. 108, pp. 111-120. ISSN 0161-5890. eISSN 1872-9142. Available under: doi: 10.1016/j.molimm.2019.02.010

@article{Mah2019-04ubiqu-45521, title={The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8+ T cells}, year={2019}, doi={10.1016/j.molimm.2019.02.010}, volume={108}, issn={0161-5890}, journal={Molecular Immunology}, pages={111--120}, author={Mah, Mei Min and Basler, Michael and Groettrup, Marcus} }

FAT10 is the only ubiquitin-like modifier which directly targets its substrate proteins for rapid degradation by the proteasome. While the conjugation and proteasomal targeting of FAT10 are fairly well understood, the biological functions of FAT10 have remained largely elusive. Here we have investigated the role of FAT10 in cytokine responses in mice upon viral infection. We used lymphocytic choriomeningitis virus (LCMV) infection of mice to induce the IFN-γ and TNF-α-dependent expression of FAT10. We found that TCR-stimulated splenocytes derived from LCMV-infected FAT10<sup>-/-</sup> mice secreted less IFN-γ and expressed less mRNA for IL-12 p40 but secreted more IFN-α and IFN-β compared to FAT10<sup>+/-</sup> mice. The reduction in IFN-γ secretion could be assigned to CD8<sup>+</sup> T cells. Nevertheless, LCMV viral clearance was similar in FAT10<sup>-/-</sup> as compared to FAT10<sup>+/-</sup> mice. Since FAT10 has previously been reported to promote influenza A virus (IAV) replication in vitro we have studied the effect of FAT10 deficiency during IAV infection in mice. Unexpectedly, IAV titers and disease symptoms were not changed in FAT10<sup>-/-</sup> mice even though the Fat10 mRNA was rapidly induced in the lung upon IAV infection. In conclusion, we find that FAT10 fine-tunes the balance of interferons during viral infection by lowering the production of type I and enhancing type II interferons. 2019-03-19T14:01:54Z eng The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8<sup>+</sup> T cells Basler, Michael 2019-04 2019-03-19T14:01:54Z Mah, Mei Min Groettrup, Marcus Basler, Michael Mah, Mei Min Groettrup, Marcus

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