Mediator of IRF3 activation (MITA, also named as STING/ERIS/MPYS/TMEM173), is essential to DNA virus-or cytosolic DNA-triggered innate immune responses. In this study, we demonstrated the negative regulatory role of RING-finger protein (RNF) 90 in innate immune responses targeting MITA. RNF90 promoted K48-linked ubiquitination of MITA and its proteasome-dependent degradation. Overexpression of RNF90 inhibited HSV-1-or cytosolic DNA-induced immune responses whereas RNF90 knockdown had the opposite effects. Moreover, RNF90-deficient bone marrow-derived dendritic cells (BMDCs), bone marrow-derived macrophages (BMMs) and mouse embryonic fibroblasts (MEFs) exhibited increased DNA virus-or cytosolic DNA-triggered signaling and RNF90 deficiency protected mice from DNA virus infection. Taken together, our findings suggested a novel function of RNF90 in innate immunity. OPEN ACCESS Citation: Yang B, Liu Y, Cui Y, Song D, Zhang G, Ma S, et al. (2020) RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation. PLoS Pathog 16(3): e1008387.

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The mAb, LA22, is a rapid, high-internalizing antibody, and this property makes it a promising vehicle for tumor-targeted drug delivery.

Abbreviations: HPA, hyperphenylalaninemia; IEM, inborn errors of metabolism; IVA, isovaleric academia; MMA, methylmalonic academia; MS/MS, tandem mass spectrometry; MSUD, maple syrup urine disease; PCD, primary carnitine deficiency; SCAD, short-chain acyl-CoA dehydrogenase deficiency. AbstractBackground: Tandem mass spectrometry is a powerful technology available in China over the last 15 years. The development of tandem mass spectrometry had made it possible to rapidly screen newborns for inborn errors of metabolism. The aim of this study was to determine the birth incidence of inborn errors of metabolism through expanded screening of newborns by tandem mass spectrometry in Xinxiang area.Methods: Dried blood spots from 50 112 newborns were assessed for inborn errors of metabolism by tandem mass spectrometry. The diagnoses were confirmed based on the clinical features, conventional laboratory tests, and the organic acid levels tested in urine by gas chromatography-mass spectrometry. Results:The study findings revealed that 31 newborns were diagnosed with inborn errors of metabolism. The total incidence rate of inborn errors of metabolism was 1/1617, and these included 16 cases of amino acid disorders (51.6%), nine cases of organic acid disorders (29.0%), and 6 (19.4%) cases of fatty acid beta-oxidation disorders. Conclusions:The screening for the incidence of inborn errors of metabolism in Xinxiang area showed that the rate was higher than previously reported. This study provides valuable data which may be useful in facilitating improvements in the expansion of screening to enable early diagnosis and treatment of inborn errors of metabolism before the onset of symptoms. K E Y W O R D S amino acid disorders, fatty acid beta-oxidation disorders, inborn errors of metabolism, organic acid disorders, tandem mass spectrometry S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.

Intestinal fungi are critical for modulating host immune homeostasis and underlying mechanisms remain unclear. We show that dendritic cell (DC)–specific deficiency of casitas B-lineage lymphoma (c-Cbl) renders mice susceptible to dextran sodium sulfate (DSS)–induced colitis. Mechanistically, we identify that c-Cbl functions downstream of Dectin-2 and Dectin-3 to mediate the ubiquitination and degradation of noncanonical nuclear factor κB subunit RelB. Thus, c-Cbl deficiency in DCs promotes α-mannan–induced activation of RelB, which suppresses p65-mediated transcription of an anti-inflammatory cytokine gene, il10, thereby aggravating DSS-induced colitis. Moreover, suppressing fungal growth with fluconazole or inhibition of RelB activation in vivo attenuates colitis in mice with DC-specific deletion of c-Cbl. We also demonstrate an interaction between c-Cbl and c-Abl tyrosine kinase and find that treatment with DPH, a c-Abl agonist, synergistically increases fungi-induced c-Cbl activation to restrict colitis. Together, these findings unravel a previously unidentified fungi-induced c-Cbl/RelB axis that sustains intestinal homeostasis and protects against intestinal inflammation.