Study Identifies Human Genes Enabling SARS-CoV-2 Infection
The activity of a gene called CIART is a key factor in the establishment of the viral infection that causes COVID-19, according to a study from researchers at Weill Cornell...
Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming - Nature Communications
Source : https://www.nature.com/articles/s41467-023-36594-x
Dysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell...
Dysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell differentiation by orchestrating metabolic and epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis and oxidative phosphorylation in Th17- and Treg-polarizing T cells. Following treatment with itaconate, the S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels are decreased by inhibiting the synthetic enzyme activities in Th17 and Treg cells, respectively. Consequently, these metabolic changes are associated with altered chromatin accessibility of essential transcription factors and key gene expression in Th17 and Treg cell differentiation, including decreased RORγt binding at the Il17a promoter. The adoptive transfer of itaconate-treated Th17-polarizing T cells ameliorates experimental autoimmune encephalomyelitis. These results indicate that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and could be a potential therapeutic agent for autoimmune diseases.
The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences - Nature Immunology
Source : https://www.nature.com/articles/s41590-023-01463-8
Cheng et al. demonstrate that an extra copy of the X-linked epigenetic regulator UTX in females increases natural killer (NK) cell effector function. As NK cells are critical for antiviral...
Viral infection outcomes are sex biased, with males generally more susceptible than females. Paradoxically, the numbers of antiviral natural killer (NK) cells are increased in males. We demonstrate that while numbers of NK cells are increased in male mice, they display decreased effector function compared to females in mice and humans. These differences were not solely dependent on gonadal hormones, because they persisted in gonadectomized mice. Kdm6a (which encodes the protein UTX), an epigenetic regulator that escapes X inactivation, was lower in male NK cells, while NK cell-intrinsic UTX deficiency in female mice increased NK cell numbers and reduced effector responses. Furthermore, mice with NK cell-intrinsic UTX deficiency showed increased lethality to mouse cytomegalovirus. Integrative multi-omics analysis revealed a critical role for UTX in regulating chromatin accessibility and gene expression critical for NK cell homeostasis and effector function. Collectively, these data implicate UTX as a critical molecular determinant of sex differences in NK cells.
Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/36922030/
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Conclusions: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.
The Pandemic Within the Pandemic: Unprecedented Rise in Alcohol-related Hepatitis During the COVID-19 Pandemic - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/34653062/
Our study revealed drastic increases in severe alcohol-related hepatitis requiring inpatient management, specifically in patients under the age of 40 and in women during the COVID-19 pandemic. Given the high...
Conclusions: Our study revealed drastic increases in severe alcohol-related hepatitis requiring inpatient management, specifically in patients under the age of 40 and in women during the COVID-19 pandemic. Given the high morbidity and mortality associated with severe alcohol-related hepatitis, these findings have far-reaching and lasting implications for our already strained health care system extending beyond the COVID-19 pandemic timeframe. Urgent public health interventions are needed to combat the rising misuse of alcohol and its consequences.
Influence of Sex on Respiratory Syncytial Virus Genotype Infection Frequency and Nasopharyngeal Microbiome - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/36815771/
Respiratory syncytial virus (RSV) has a significant health burden in children, older adults, and the immunocompromised. However, limited effort has been made to identify emergence of new RSV genotypes' frequency...
Importance: Overall, we show sex differences in RSV genotype-nasopharyngeal microbiome, suggesting an interaction host genetics-virus-microbiome interaction.