Shawn J. Green’s Post

Lecture: Immunology in Cardiometabolic Disease: The understanding of cardiovascular disease (CVD) has traditionally focused on factors such as high blood pressure and elevated cholesterol levels. However, emerging research has highlighted the critical involvement of the immune system, especially chronic low-grade inflammation, in the development and progression of CVD. Numerous factors can contribute to low-grade inflammation including diet, obesity, and diabetes. Chronic inflammation is a risk factor for CVD where it especially promotes the progression of atherosclerosis. Individuals at risk of CVD are often treated with lipid-lowering drugs, which reduces the risk of cardiovascular events with by approx. 30%. Evidence suggests that the residual risk is linked to inflammation, calling for the need to develop effective and safe anti-inflammatory strategies for the prevention and treatment of CVD.

The role of high cholesterol in SARS-CoV-2 infectivity. Scripps Research Institute, Jupiter, Florida and University of Utah Health Sciences Center, Salt Lake City, Utah. Journal of Biological Chemistry (jbc): Research Article. Volume 299, Issue 6, 104763, June 2023. Overview: Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2. The virus binds to angiotensinogen converting enzyme 2 (ACE2), which mediates viral entry into mammalian cells. COVID-19 is notably severe in the elderly and in those with underlying chronic conditions. The cause of selective severity is not well understood. Here we show cholesterol and the signaling lipid phosphatidyl-inositol 4,5 bisphosphate (PIP2) regulate viral infectivity through the localization of ACE2’s into nanoscopic (<200 nm) lipid clusters. Key: Uptake of cholesterol into cell membranes (a condition common to chronic disease) causes ACE2 to move from PIP2 lipids to endocytic ganglioside (GM1) lipids, where the virus is optimally located for viral entry. In mice, age and high-fat diet increase lung tissue cholesterol by up to 40%. And in smokers with chronic disease, cholesterol is elevated 2-fold, a magnitude of change that dramatically increases infectivity of virus in cell culture. We conclude increasing the ACE2 location near endocytic lipids increases viral infectivity and may help explain the selective severity of COVID-19 in aged and diseased populations. https://lnkd.in/eDvW3qKK

Impact of Obesity on the IL-6 Immune Marker and Th17 Immune Cells in C57BL/6 Mice Models with Imiquimod-Induced Psoriasis body fat is an endocrine producer So Hee Park 1, Kyung Ah Lee 2, Jae-Hyeog Choi 3, SaeGwang Park 4, Dae-Wook Kim 5, So Young Jung 1 Affiliations expand PMID: 36982669 PMCID: PMC10059802 DOI: 10.3390/ijms24065592 Free PMC article Abstract Obese psoriatic patients experience higher disease severity and exhibit poorer treatment responses and clinical outcomes. It has been proposed that proinflammatory cytokines produced by adipose tissue exacerbate psoriasis; however, the role of obesity in psoriasis remains unclear. This study aimed to elucidate the role of obesity in the pathogenesis of psoriasis, focusing on immunological changes. To induce obesity, mice were fed a high-fat diet for 20 weeks. We then applied imiquimod to the skin on a mouse's back for seven consecutive days to induce psoriasis and scored lesion severity every day for seven days. Cytokine levels in serum and the Th17 cell population in the spleen and draining lymph nodes were studied to identify immunological differences. The clinical severity was more remarkable, and histologically the epidermis was also significantly thicker in the obese group. Increased levels of IL-6 and TNF-α were observed in serum after psoriasis. They were elevated to a greater degree, with greater expansion of the functional Th17 cell population in the obese group. It is concluded that obesity could exacerbate psoriasis through mechanisms that involve elevated proinflammatory cytokine secretion and an expanded Th17 cell population.

🌟 Fasting-Mimicking Diet (FMD) Shows Promise in Combating Colorectal Cancer in Mice! 🌟 🔬 𝐒𝐭𝐮𝐝𝐲 𝐇𝐢𝐠𝐡𝐥𝐢𝐠𝐡𝐭𝐬: A recent study published that a 4-day Fasting-Mimicking Diet (FMD) can significantly suppress mouse colorectal cancer (CRC) progression. This diet reduced tumour growth, enhanced immune responses, and positively remodelled gut microbiota. 🦠 𝐊𝐞𝐲 𝐅𝐢𝐧𝐝𝐢𝐧𝐠𝐬: • 𝐓𝐮𝐦𝐨𝐫 𝐒𝐮𝐩𝐩𝐫𝐞𝐬𝐬𝐢𝐨𝐧: FMD cycles delayed CRC tumour growth and reduced tumour weight by an impressive 57%. • 𝐈𝐦𝐦𝐮𝐧𝐞 𝐁𝐨𝐨𝐬𝐭: Increased tumour-infiltrating lymphocytes, particularly CD8+ T cells, were observed. • 𝐆𝐮𝐭 𝐇𝐞𝐚𝐥𝐭𝐡: FMD stimulated the growth of beneficial gut bacteria, especially Lactobacillus johnsonii. • 𝐒𝐲𝐧𝐞𝐫𝐠𝐲 𝐰𝐢𝐭𝐡 𝐈𝐦𝐦𝐮𝐧𝐨𝐭𝐡𝐞𝐫𝐚𝐩𝐲: Combining FMD with anti-PD-1 therapy resulted in a more effective inhibition of CRC progression. 💡 This study underscores the potential of dietary interventions in cancer treatment. The FMD provides a feasible alternative to traditional fasting and shows promise in enhancing the efficacy of existing cancer therapies. 👥 What Are Your Thoughts? As we continue to explore the intersection of diet and health, studies like these highlight the importance of innovative approaches to disease prevention and treatment. Do you think dietary interventions like FMD could revolutionize cancer therapy? Share your thoughts in the comments! https://lnkd.in/gJP7nbQa #cancerresearch #dietaryinterventions #fastingmimickingdiet #guthhealth #Immunotherapy #colorectalcancer #scientificbreakthroughs #healthInnovation

Non-human primate model of long-COVID identifies immune associates of hyperglycemia Abstract Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects. Continued....click on the image in the banner below to access entire study results, its authors and their references. Posted by Larry Cole

The IL-17 cytokine family plays diverse roles in immune regulation, inducing proinflammatory responses and allergic reactions by stimulating various immune signaling molecules. It promotes the production of cytokines, chemokines, and prostaglandins from different cell types, contributing to inflammation. IL-17 misregulation is associated with psoriasis, autoimmune encephalitis, rheumatoid arthritis, asthma, lupus, and anti-tumor immunity. It is also essential for the function of T helper 17 cells. We offer numerous humanized IL-17 mouse models, which can be used to evaluate therapeutic candidates for inflammatory diseases caused by aberrant IL-17  expression, such as psoriasis(https://lnkd.in/ergBPPsC) and experimental autoimmune encephalomyelitis (EAE)(https://lnkd.in/e6Uyhf-X). Check out our B-hIL17A Mice: https://lnkd.in/dKpGWZsh #preclinicalresesarch #mousemodel #pharmacology #diseasemodel #immunooncology #immunotherapy #therapeutics #antitumortherapy #cancertherapy #cancerresearch #inflammatory #metabolicdisease

Back to the basics; sort of. Fundamentals matter and intervention of the IL23 pathway comes with a ton of solid validation; think Stelara and Skyrizi and Tremfya. Those are all injectable Biologics and what distinguishes JNJ-2113, arising from the Protagonist-JNJ collaboration, is that it’s a first-in-class Oral peptide IL23 receptor antagonist. Multiple clinical trials currently underway in different indications. Protagonist Therapeutics

Resident memory T cells (TRMs) help control local immune homeostasis and contribute to tissue protective immune responses. In this work, Jim Arthos´ group demonstrate that MAdCAM-1, a ligand for the gut homing receptor α4β7 integrin, in the presence of retinoic acid and TGF-β provide a costimulatory signal that induces blood CD8+ T cells to adopt a TRM-like phenotype. These cells express CD103 (integrin αE) and CD69, the two major TRM cell surface markers, along with CD101. They also express CCR5, CCR9 and α4β7, three receptors associated with gut homing. This report advances our understanding of the signals that drive the differentiation of CD8+ T cells into TRMs and provides a means to expand these cells in vitro, thereby affording an avenue to generate more effective tissue specific immunotherapies. Congratulations to Alexandre Girard and the whole team at National Institute of Allergy and Infectious Diseases (NIAID) led by James Arthos and Claudia Cicala, to Livia Goes at Instituto Nacional de Câncer and to all collaborators at Walter Reed in Bangkok, National Cancer Institute (NCI) and Northwestern University - The Feinberg School of Medicine for the elegant work published! https://lnkd.in/dKnPmQMr

Vitamin D has numerous effects on cells within the immune system. It inhibits B cell proliferation and blocks B cell differentiation and immunoglobulin secretion. Vitamin D additionally suppresses T cell proliferationand results in a shift from a Th1 to a Th2 phenotype. Furthermore, it affects T cell maturation with a skewing away from the inflammatory Th17 phenotype and facilitates the induction of T regulatory cells. These effects result in decreased production of inflammatory cytokines (IL-17, IL-21) with increased production of anti-inflammatory cytokines such as IL-10 . Vitamin D also has effects on monocytes and dendritic cells (DCs). It inhibits monocyte production of inflammatory cytokines such as IL-1, IL-6, IL-8, IL-12 and TNFα During my visits I discovered that many cardiologists & pulmonologists recommended patients to take Vitamin D for booting their immunity that it decreases the risk of respiratory infection as it decreases the fluids on chest & it is also extremely important for blood vessels & heart function

Metabolic disturbances may contribute to to uncontrolled autoreactive T cells and B cells in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA): 🔸 Glycolytic influx and oxidative phosphorylation are enhanced in SLE T cells, leading to proinflammatory T cell responses. 🔸 RA T cells exhibit impaired mitochondrial function and enhanced fatty acid metabolism, allowing their tissue-invasive and proinflammatory nature. 🔸 Fatty acid oxidation is enhanced in SLE B cells and promotes germinal center responses, resulting in autoantibody production. A better understanding about how metabolic reprogramming determines the autoreactive and proinflammatory nature of lymphocytes in these disorders may provide of new therapeutic targets. 🔗https://lnkd.in/dDHeyGkJ