Human caspase‐4 and its mouse homolog caspase‐11 are receptors for cytoplasmic lipopolysaccharide. Activation of the caspase‐4/11‐dependent NLRP3 inflammasome is required for innate defense and endotoxic shock, but how caspase‐4/11 is modulated remains unclear. Here, we show that mice lacking the oxidative stress sensor glutathione peroxidase 8 (GPx8) are more susceptible to colitis and endotoxic shock, and exhibit reduced richness and diversity of the gut microbiome. C57BL/6 mice that underwent adoptive cell transfer of GPx8‐deficient macrophages displayed a similar phenotype of enhanced colitis, indicating a critical role of GPx8 in macrophages. GPx8 binds covalently to caspase‐4/11 via disulfide bonding between cysteine 79 of GPx8 and cysteine 118 of caspase‐4 and thus restrains caspase‐4/11 activation, while GPx8 deficiency leads to caspase‐4/11‐induced inflammation during colitis and septic shock. Inhibition of caspase‐4/11 activation with small molecules reduces the severity of colitis in GPx8‐deficient mice. Notably, colonic tissues from patients with ulcerative colitis display low levels of Gpx8 and high caspase‐4 expression. In conclusion, these results suggest that GPx8 protects against colitis by negatively regulating caspase‐4/11 activity.

Although the PVR/TIGIT immune checkpoint axis has been suggested as a promising target for cancer immunotherapy and multiple TIGIT-targeting therapies are undergoing clinical trials, the underlying regulatory mechanisms of PVR/TIGIT interaction remain inconclusive. Here we show that TIGIT N-glycosylations are critical for maintaining the interaction between TIGIT and PVR. TIGIT has two N-glycosylation residues, N32 and N101. N-glycosylation on N101 of TIGIT and, to less extent, on N32, play potent roles in PVR binding. Taken together, these findings suggest that the N-glycosylation sites on TIGIT, especially residue N101, may be potential targets for PVR/TIGIT immune checkpoint blockade.

With almost no community-transmitted cases and without any complete lockdown throughout 2020, Taiwan is one of very few countries worldwide that has recorded minimal impact from the COVID-19 pandemic attack. This is despite being only 130 km from China and having frequent business communications with that country, where COVID-19 first emerged. At the end of December 2020, Taiwan had recorded just 873 cases and 7 deaths, in a country of around 24 million people. How to determine the effectiveness of public health policies is an important issue that must be resolved, especially in those countries that have experienced few cases of community-transmitted COVID-19. Our analysis of epidemiological data in Taiwan relating to influenza-like illness (ILI), enterovirus and diarrhoea from the past 3 years reveals dramatic reductions in the incidence of ILI and enterovirus in 2020, compared with 2018 and 2019. These reductions occurred within 2 weeks of the government issuing public health policies for COVID-19 and indicate that such policies can effectively reduce infectious diseases overall. In contrast, no such reduction in ILI activity was observed in 2020 after the first COVID-19 case was reported in the USA. We suggest that infectious diseases data can be used to inform effective public health policies needed to break the transmission chain of COVID-19 and that ongoing monitoring of infectious diseases data can provide confidence about nationwide health.

Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 μg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 μg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients.

An efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) appears to be crucial for controlling and resolving this viral infection. However, many studies have reported autoimmune characteristics in severe COVID-19 patients. Moreover, clinical observations have revealed that COVID-19-associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)-ILD. This study explored this phenomenon by seeking to identify and characterize myositis-specific and related autoantibodies in 25 COVID-19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID-19 with one or more autoantibodies against several myositis-related antigens (Jo-1, Ku, Mi-2 beta, PL-7, PL-12, PM-Scl 75, PM-Scl 100, Ro-52, and SRP); no anti-MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which [S-35]methionine-labeled K562 cellular antigens were precipitated and visualized by gel electrophoresis. This result was confirmed by an immunoprecipitation assay and immunoblotting; 2 patients exhibited anti-Ku70 and anti-Ku80 antibodies. Our data suggest that it is necessary to use more than one method to characterize and evaluate autoantibodies in people recovered from COVID-19, in order to avoid misinterpreting those autoantibodies as diagnostic markers for autoimmune diseases.