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Imaging Study Reveals Viral RNA Persists for Years in Tissues of Long COVID Patients PET imaging reveals long COVID patients can possess leftover SARS-CoV-2 RNA in the gut years after infection.   By Blake Forman Long COVID patients display signs of abnormal immune cell activation and possess leftover SARS-CoV-2 RNA in the gut, a study published in the journal Science Translational Medicine has found. The findings add to mounting evidence that viral persistence and sustained immune activation are key factors underpinning long COVID symptoms. Imaging reveals a hiding place for SARS-CoV-2 RNA The term “long COVID” refers to a diverse group of symptoms that can persist in people who have recovered from infection with SARS-CoV-2. Common symptoms range from fatigue, shortness of breath and brain fog to heart disease. Survey data from one study has suggested that an estimated 18 million US adults could be living with long COVID. Despite this burden, there are still no approved treatments for the condition more than 4 years since the COVID-19 pandemic began. Data regarding SARS-CoV-2 persistence in non-blood tissues are sparse, with clinical studies in living individuals involving limited tissue quantities obtained through non-invasive biopsies. Additionally, sites of interest for studying SARS-CoV-2 persistence such as the brain, spinal cord and heart cannot be sampled in living individuals. “There has been a large amount of inferential data supporting a view that a key factor underpinning long COVID may be that some people do not properly clear the virus and harbor reservoirs of SARS-CoV-2 in their tissues,” said Danny Altmann, professor of immunology at Imperial College London. “It’s been hard to prove this case – evidence has come from a small number of studies in which long Covid symptoms were correlated with presence of virus analyzed from gut biopsies.” Continued.....please click on image in banner below to access and finish reading this piece. Posted by Larry Cole

USC Scientists Uncover Secret to a Youthful Immune System By Keck School of Medicine of USCOctober 28, 2024 "Gene Activity in Delayed and Early Agers In delayed agers, the subset of blood stem cells decreased their production of innate immune cells, protecting against the effects of aging. Among delayed agers, there was an increase in gene activity related to blood stem cells’ regulation and response to external signals—which might keep their production of innate immune cells in check. When the scientists used CRISPR to edit out these genes, blood stem cells reversed their natural tendency and produced more innate immune cells instead of adaptive immune cells—like in the early agers. In contrast, in early agers, the subset of blood stem cells shifted towards producing more innate immune cells, which, in excess, lead to many diseases of aging. Accordingly, in these early agers, the scientists found an increase in gene activity related to the proliferation of blood stem cells and the differentiation of innate immune cells. When the scientists used CRISPR to edit out these early aging genes, blood stem cells produced more adaptive immune cells instead of innate immune cells—becoming more similar to those in the delayed agers. Importantly, delayed agers tended to live longer than early agers. “In the elderly human population, the immune system often tips into producing an overabundance of innate immune cells, which can contribute to diseases such as myeloid leukemia and immune deficiencies,” said Nogalska, senior scientist and lab manager in the Lu Lab. “Our study suggests how we might promote a more youthful immune system to combat these common diseases of aging.”" "Reference: “Age-associated imbalance in immune cell regeneration varies across individuals and arises from a distinct subset of stem cells” by Anna Nogalska, Jiya Eerdeng, Samir Akre, Mary Vergel-Rodriguez, Yeachan Lee, Charles Bramlett, Adnan Y. Chowdhury, Bowen Wang, Colin G. Cess, Stacey D. Finley and Rong Lu, 24 October 2024, Cellular & Molecular Immunology. DOI: 10.1038/s41423-024-01225-y"

Exciting breakthrough in understanding human immunity across lifespan. Groundbreaking study just published in Nature Immunology has created the first-ever comprehensive map of how our immune system changes from birth to old age. The authors analyzed immune cells from 220 healthy individuals aged 0-90+ years using cutting-edge multiomics. - First complete timeline of immune system development and aging - T cells show the most dramatic age-related changes - Identified a previously unknown type of B cells in children - They developed a model to predict "immune age" check the article here: https://lnkd.in/etbfX_76

How heat from fever and inflammation affects immune cells Scientists showed that fever temperatures boost activity in certain immune cells but also promote DNA damage. The findings suggest how chronic inflammation might contribute to cancer risk. Fevers may help us fight disease, but might also contribute to cancer risk. Fever raises the temperature of the body, and local inflammation can raise the temperature of surrounding tissues. But it’s not clear how these temperature changes affect the immune cells that fight infection and mediate inflammation. Among the most critical cells in the immune response are T cells. A variety of T cell types with different functions help recognize pathogens, control inflammation, and kill infected cells. A team of researchers, led by Dr. Jeffrey Rathmell at Vanderbilt University Medical Center, carefully examined how higher temperatures affect T cells. The results of the study, which was funded in part by NIH, appeared in Science Immunology on September 20, 2024. The team cultured mouse T cells at a normal body temperature (37 °C or 98.6 °F) and at fever temperature (39 °C or 102.2 °F). At the higher temperature, T helper cells, which direct other immune cells by releasing signaling molecules called cytokines, produced more cytokines than at the lower temperature. At the same time, regulatory T cells, which suppress immune responses, were less effective at the higher temperature. All the types of T cells evaluated proliferated more at the higher temperature. These led to an enhanced inflammatory state at fever temperature. Higher temperatures also enhanced metabolism in various types of T cells. The exception was in the T helper 1 (TH1) cell subset, whose metabolic rate was largely unaffected. TH1 cells developed stress and DNA damage at high temperature, making them less likely to survive. Those that did survive, however, had more mitochondria—the energy-generating compartments of the cell—and greater activity. Further experiments showed that higher temperatures impaired a protein called electron transport chain complex 1 (ETC1) in TH1 cells. ETC1 is part of the process by which mitochondria convert fuel to energy. Impairing ETC1 led to formation of reactive byproducts, mitochondrial stress, and DNA damage. In response, the cells activated mechanisms to repair DNA or, failing that, to self-destruct. Sequencing data from patients with Crohn’s disease and rheumatoid arthritis, two inflammatory autoimmune diseases. They found signs of increased DNA damage and ETC1 impairment in TH1 cells like they saw in the cultured cells. These findings suggest how fever and inflammation can enhance the immune response, but also increase DNA damage. DNA damage results in mutations when the damage isn’t properly repaired. This could explain why chronic inflammation increases the risk of cancer. —by Brian Doctrow, Ph.D.

The League of Extraordinary Cell Types – Blood: B cells 🅱️ B cells, aka B lymphocytes, are immune cells that drive our body’s adaptive immune response. What’s that? The second line of defense that is activated when phagocytosis is not sufficient for combatting an invading pathogen. 🐘 Plasma B cells mount the adaptive immune response by producing and releasing antibodies against an invading pathogen. Memory B cells, like elephants, have an excellent memory: they remember the antigens of past invading pathogens so that they can activate the immune response if the same pathogen visits the body again. 🌀 B cells are derived from the bone marrow from hematopoietic stem cells. Each immature B cell is equipped with a B cell antigen receptor (BCR), allowing it to have a unique antigen specificity. This results from a process called V(D)J recombination, a process that, nevertheless, results in the generation of up to 75% of autoreactive species which can, subsequently, generate autoimmune diseases. 🚩 Central tolerance mechanisms keep B cell BCR autoreactivity under control through the deletion of autoreactive B cells by apoptosis, ‘anergy’ by which autoreactive B cells become unresponsive to antigens and eventually die, or ‘receptor editing’, by which antibody light chain genes undergo rearrangements. ⚔️ B cells can act as a double-edged sword in the immune response; while B cells benefit our immune system by providing it with memory, they can also turn their ‘weapons’ against the body itself, resulting in autoimmune diseases (such as rheumatoid arthritis and lupus erythematosus) or cancer. Stay tuned to learn more extraordinary cell types! Credit: Art by Nelli Aghekyan, Set in motion by Emanuele Petretto, PhD , Words by Semeli Platsaki, PhD Project Coordinator: Małgorzata Maksymowicz, PhD, Series Director: Dr. Radhika Patnala #scicomm #lifescience #Extraordinarycelltypes About the series: The League of Extraordinary Cell Types The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types that make our bodies tick ❤.  ____________________________________________ Tag someone you know working in this field and help us find them 😊 If you enjoyed this content, make sure to follow us not to miss a post!

The League of Extraordinary Cell Types – Blood: B cells 🅱️ B cells, aka B lymphocytes, are immune cells that drive our body’s adaptive immune response. What’s that? The second line of defense that is activated when phagocytosis is not sufficient for combatting an invading pathogen. 🐘 Plasma B cells mount the adaptive immune response by producing and releasing antibodies against an invading pathogen. Memory B cells, like elephants, have an excellent memory: they remember the antigens of past invading pathogens so that they can activate the immune response if the same pathogen visits the body again. 🌀 B cells are derived from the bone marrow from hematopoietic stem cells. Each immature B cell is equipped with a B cell antigen receptor (BCR), allowing it to have a unique antigen specificity. This results from a process called V(D)J recombination, a process that, nevertheless, results in the generation of up to 75% of autoreactive species which can, subsequently, generate autoimmune diseases. 🚩 Central tolerance mechanisms keep B cell BCR autoreactivity under control through the deletion of autoreactive B cells by apoptosis, ‘anergy’ by which autoreactive B cells become unresponsive to antigens and eventually die, or ‘receptor editing’, by which antibody light chain genes undergo rearrangements. ⚔️ B cells can act as a double-edged sword in the immune response; while B cells benefit our immune system by providing it with memory, they can also turn their ‘weapons’ against the body itself, resulting in autoimmune diseases (such as rheumatoid arthritis and lupus erythematosus) or cancer. Stay tuned to learn more extraordinary cell types! Credit: Art by Nelli Aghekyan, Set in motion by Emanuele Petretto, PhD , Words by Semeli Platsaki, PhD Project Coordinator: Małgorzata Maksymowicz, PhD, Series Director: Dr. Radhika Patnala #scicomm #lifescience #Extraordinarycelltypes About the series: The League of Extraordinary Cell Types The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types that make our bodies tick ❤.  ____________________________________________ Tag someone you know working in this field and help us find them 😊 If you enjoyed this content, make sure to follow us not to miss a post!

Interesting Article: New Complete Human Immune System in Mice Scientists at The University of Texas Health Science Center at San Antonio have created a new mouse model, named TruHuX (for truly human, or THX), with a fully functional human immune system and human-like gut microbiome. This development, led by Dr. Paolo Casali, represents a significant advancement in the field. Key Highlights: - Complete Human Immune System: The THX mice possess fully developed human lymph nodes, thymus, T and B lymphocytes, and memory B cells, enabling them to mount specific antibody responses similar to humans. - Advanced Immunotherapy Research: These mice can respond to vaccines like the Pfizer COVID-19 mRNA vaccine and develop autoimmunity (Lupus model), making them ideal for studying human immune responses and developing new immunotherapies. 💡 Impact: This innovation opens new avenues for in vivo human experimentation, the development of cancer immunotherapies, human bacterial and viral vaccines and autoimmune diseases. Comparison with other Humanized Mice Models: THX mice show improved B cell development, enhanced memory B cell formation and produce more human-like antibody responses compared to other models. 🔗 Read the full article here: https://lnkd.in/e2pKgX6t #MiceModel #Immunotherapy #Innovation #ScientificBreakthrough #HumanizedMice #ImmuneSystemResearch #DiseaseModeling #VaccineDevelopment

Engineered immune cells may be able to tame inflammation by University of California, San Francisco "When the immune system overreacts and starts attacking the body, the only option may be to shut the entire system down and risk developing infections or cancer. But now, scientists at UC San Francisco may have found a more precise way to dial the immune system down. The technology uses engineered T cells that act as immune "referees" to soothe overreacting immune responses. They also can mop up inflammatory molecules. The new approach could be used to stop the body from rejecting transplanted organs and tissues, such as pancreatic islet cells, which are sometimes used to treat type 1 diabetes. That way, recipients would not need to take harsh immunosuppressant drugs. "This technology can put the immune system back into balance," said Wendell Lim, Ph.D., UCSF professor of cellular and molecular pharmacology and co-senior author of the paper, which appears Dec. 5 in Science. "We see it as a potential platform for tackling all kinds of immune dysfunction." Lim and his colleagues were inspired by "suppressor" cells, which are the immune system's natural brakes. They wanted to take advantage of these suppressor cells' power to temper immune responses, such as inflammation. Unfortunately, suppressor cells can't always stop a dangerous immune response. In type 1 diabetes, for example, the immune system destroys pancreatic islet cells, while these suppressor cells just stand by. The team adapted the suppressor cells' anti-inflammatory abilities to work in CD4 immune cells. These are the same cells that are used to make cancer-killing CAR T cells. They also gave these cells a molecular sensor to guide them to their target tissue in the body. [...]" "More information: Nishith R. Reddy et al, Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs, Science (2024). DOI: 10.1126/science.adl4793. https://lnkd.in/g8HzABcJ Journal information: Science "

In a time where emphasis is put on reducing the necessity of animal experimentation for laboratory research, I really do believe the utilisation of complex 3D in vitro models can propel research forward in the drug discovery domain. Fascinating work showing the incorporation of autologous immune cells in patient organoids! 👏

Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation and immunosuppression is a crucial feature of sepsis immunity. Epigenetic modifications, including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNA, play essential roles in regulating sepsis immunity through epi-information independent of the DNA sequence. In recent years, the mechanisms of histone modification in sepsis have received increasing attention, with ongoing discoveries of novel types of histone modifications. Due to the capacity for prolonged effects on immune cells, histone modifications can induce immune cell reprogramming and participate in the long-term immunosuppressed state of sepsis. Herein, we systematically review current mechanisms of histone modifications involved in the regulation of sepsis, summarize their role in sepsis from an immune perspective and provide potential therapeutic opportunities targeting histone modifications in sepsis treatment. FACTS: Histone modification is an essential part of epigenetic modifications, with generally revealed enzyme system and increasingly well-understood regulatory mechanism. Immune remodeling is one of the hallmarks of sepsis regulated synergistically or individually by various epigenetic factors. Histone modification pathway involves in the immune remodeling of sepsis and plays a role in different stages of septic immunity. Preclinical interventions targeting histone modifications have exhibited effectiveness in treating sepsis and relieving multiple organ dysfunction due to sepsis.