Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class II–restricted epitopes, we found that myosin heavy chain α (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in Balb/c mice. Transferred MYHCA614–629-specific CD4+ T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lymph nodes (med-LNs) of infarcted mice, acquired a Treg phenotype with a distinct prohealing gene expression profile, and mediated cardioprotection. Myocardial Tregs were also detected in autopsy samples from patients who had had a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in patients with MI. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence that MI context induces prohealing T cell autoimmunity in mice and confirm the existence of an analogous heart/med-LN/T cell axis in patients with MI.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

Related Links:

We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72Ô...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, a significant (30%) increase in maximum lifespan of mice was found after nonablative transplantation of 100 million nucleated bone marrow (BM) cells from young donors, initiated at the age that is equivalent to 75 years for humans. Moreover, rejuvenation was accompanied by a high degree of BM chimerism for the nonablative approach. Six months after the transplantation, 28% of recipients' BM cells were of donor origin. The relatively high chimerism efficiency that we found is most likely due to the advanced age of our recipients having a depleted BM pool. In addition to the higher incorporation rates, ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, activation of pDCs and glandular epithelial cells by external or endogenous triggers induce the production of type I IFN through TLRs. Type I IFN will lead to BAFF release and activation of B cells with consequent auto-antibody production. Moreover, type I IFN may directly activate T cells which secrete pro-inflammatory cytokines, thus contributing to induce a pro-inflammatory environment. In this scenario, a feedback loop may be postulated between IFN-α production and immune complex formation which will amplify the effect of activated type I IFN system on onset or perpetuation of SS. Role of Chemokin...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
WIRED Health, now in its sixth year, returned to London’s Francis Crick Institute. The event was opened by Crick Institute director Paul Nurse who introduced the institute and its mission to understand the fundamental biology of human heal...
Source: Medgadget - Category: Medical Devices Authors: Tags: Exclusive Medicine Public Health Society Source Type: blogs
This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. Intron Retention via Alternative Splicing as a Signature of Aging https://www.fightaging.org/archives/2019/03/intron-retention-via-alternative-splicing-as-a-signature-of-aging/ In recent years researchers have inv...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study showed that potential vicious cycles underlying ARDs are quite diverse and unique, triggered by diverse and unique factors that do not usually progress with age, thus casting doubts on the possibility of discovering the single molecular cause of aging and developing the single anti-aging pill. Rather, each disease appears to require an individual approach. However, it still cannot be excluded that some or all of these cycles are triggered by fundamental processes of aging, such as chronic inflammation or accumulation of senescent cells. Nevertheless, experimental data showing clear cause and effect relationships...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, scientists screened cells from old animals to identify any RBPs that change upon aging. The screening showed that one particular protein, Pumilio2 (PUM2), was highly induced in old animals. PUM2 binds mRNA molecules containing specific recognition sites. Upon its binding, PUM2 represses the translation of the target mRNAs into proteins. Using a systems genetics approach, the researchers then identified a new mRNA target that PUM2 binds. The mRNA encodes for a protein called Mitochondrial Fission Factor (MFF), and is a pivotal regulator of mitochondrial fission - a process by which mitochondria break u...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, this is the first report to show that pyroptotic cell death occurs in the aging brain and that the inflammasome can be a viable target to decrease the oxidative stress that occurs as a result of aging. Reducing Levels of Protein Manufacture Slows Measures of Aging in Nematodes https://www.fightaging.org/archives/2018/12/reducing-levels-of-protein-manufacture-slows-measures-of-aging-in-nematodes/ Researchers here demonstrate that an antibiotic slows aging in nematode worms, providing evidence for it to work through a reduction in protein synthesis. Beyond a slowing of aging, one of the con...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
More News: Autoimmune Disease | Biomedical Science | Cardiology | Gastroschisis Repair | Genetics | Heart | Heart Attack | Study