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

Molecular Immunology
Mei Min MahMarcus Groettrup

Abstract

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-/- mice secreted less IFN-γ and expressed less mRNA for IL-12 p40 but secreted more IFN-α and IFN-β compared to FAT10+/- mice. The reduction in IFN-γ secretion could be assigned to CD8+ T cells. Nevertheless, LCMV viral clearance was similar in FAT10-/- as compared to FAT10+/- 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-/- mice even though the Fat10 mRNA was rapidly induced in the lung upon IAV infection. In conclusion, we find that FAT10 fine-tunes the bal...Continue Reading

Citations

Jun 18, 2020·Journal of Cell Science·Richard SchregleMarcus Groettrup
Jun 27, 2020·Biomolecules·Mei Min MahMarcus Groettrup
Jul 29, 2020·Journal of Cell Science·Annette Aichem, Marcus Groettrup
Sep 19, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Kai ZhangLanfang Li
Nov 24, 2019·Molecular Immunology·Michal Kandel-KfirYehuda Kamari
May 22, 2021·Trends in Microbiology·Dirk SchlüterMichael Naumann

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