Susceptibility to certain autoimmune diseases increases with age; however, mechanisms linking aging and increased susceptibility are incompletely understood. One hallmark of the aging immune system is atrophy of the thymus, the primary site of T lymphocyte generation. We and others have previously shown that aging is also associated with declines in critical thymic functions, including expression of tissue restricted self-antigen (TRA) genes, many of which are regulated by the autoimmune regulator, Aire. TRA expression in the thymus allows T cells to be tolerized to antigens typically expressed in peripheral tissues, and declining TRA expression is predicted to contribute to diminished T cell tolerance in aging. Medullary thymic epithelial cells (mTECs) had been regarded as the sole source of thymic TRA expression, but it is now clear that a subset of thymic B (tB) cells also express Aire and mediate tolerance to Aire-dependent self-antigens. Recently, we found that expression of Aire and Aire-dependent self-antigens declines in tB cells in aged mice and humans, which is also predicted to diminish central T cell tolerance induction. To test these predictions, we used MHCII tetramers to detect T cells recognizing a model TRA expressed in mTECs, Apolipoprotein B (Apob, an auto-antigen involved in atherosclerosis), in the thymus and secondary lymphoid organs of aged mice. We find that the frequency of potentially auto-reactive ApoB-specific T cells increases beginning at 6 months of age. Ongoing experiments will address whether there are similar increases in T cells specific for other TRAs, including Titin (Ttn), an autoantigen involved in late onset myasthenia gravis.
Introduction: Streptococcus mutans and S. sobrinus are the main causative agents of human dental caries. Objective: To analyze the literature on different genera of Streptococcus such as S. mutans, S. gordonii, S. sanguis, S. sobrinus and S. salivarius in relation to orthodontics.Methodology: Articles on the subject published through the PubMed, SCOPUS and Google Academic databases were analyzed, with an emphasis on the last 5 years. It was carried out with the words "Streptococcus mutans", "S. gordonii", "S. sanguis", "S. sobrinus ", "S. salivarius". Results: S. mutans: produces dental caries and demineralization of the enamel. It can be controlled with proper brushing techniques and oral hygiene. S. gordonii: predominates in the oral microflora and triggers cariogenic biofilms, is present in the formation of white spots around brackets and its development can be inhibited with fluoride-containing rinses. S. sanguis: present in orthodontic appliances, they have adverse effects that help the formation of dental plaque, mouthwash with nanio TiO2 and a good mechanical and chemical cleaning help to eliminate them. S. sobrinus: forms white spots, demineralizes enamel and causes dental caries. S. salivarius: its acid-base physiology plays an important role, the use of orthodontic appliances can produce an increase in bacteria which is associated with metal alloys. Conclusion: Streptococcus species are a problem in orthodontics, they can be eliminated by using Enlight composite resin, 0.02% chlorhexidine rinses, mouthwash with nanioTiO2 and a good mechanical and chemical brushing technique.
Introduction: During the last decades, there was a great interest in the development of bioactive dental material with the ability to interact and induce dental tissues. Biodentine is a calcium silicate-based cement that has beneficial effects on pulp cells and promotes the formation of tertiary dentin. Aim: To analyze the literature on biodentine, as well as its antimicrobial activity, its setting capacity, its clinical applications and its biological properties. Methodology: Using the keywords biodentine, root canal sealing materials, epidemiology, diagnosis, clinical manifestations, antimicrobial resistance, and treatment, the MEDLINE/PubMed and Science Direct databases were searched, with emphasis on the last 5 years. It was evaluated with the PRISMA and AMSTAR-2 guidelines. Results: The antimicrobial activity of Biodentine has been greater against strains such as Streptococcus sanguis, Enterococcus faecalis, Escherichia coli and Candida albicans. Biodentine has benefits such as excellent sealability, biocompatibility, good dimensional stability with the advantage of a setting time of 12 to 13 minutes, less than MTA. Materials used in the vital pulp method must have biocompatibility and bioactivity to promote pulp cell activity. Biodentine induces the differentiation of pulp cells into odontoblast-like cells, formation of mineralized tissue and restorative dentin. Conclusion:The composition and its applications have shown sufficient basis to perform an adequate antimicrobial activity, as well as its setting time improved to 12 minutes. Vital pulp therapy is one of the main uses of this material as it is a widely accepted material for dentin tissues due to its high biological compatibility.
T lymphocytes develop in the thymus, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells (TSCs) directs progenitors along a well-characterized differentiation program. However, the biology of stromal cells comprising the lymphopoietic thymic microenvironment remains relatively under-characterized because stromal cells are rare and difficult to isolate. Using a deconvolution technique to study gene expression essentially in situ, we previously identified a deficiency in the peroxide quenching enzyme catalase (CAT) in thymic stromal cells, and found that CAT deficiency results in high reactive oxygen species (ROS) levels in this population, eventually leading to thymic atrophy in aged mice. Here, we find that when catalase deficiency is complemented by overexpression targeted to mitochondria in transgenic mice (mCAT Tg), both ROS levels and stromal function decline in young mice relative to non-transgenic littermates. TSC transcriptome analysis reveals decreased expression of tissue-restricted antigen (TRA) and autophagy pathway genes in mCat Tg mice. Analysis of autophagy flux reporter mice ubiquitously expressing the RFP-EGFP-LC3 fusion transgene also indicates diminished autophagic flux in mCAT Tg mice, particularly in TSCs. Stromal TRA expression and autophagic flux are required for self-antigen presentation, and therefore promote negative selection of potentially auto-reactive T cells. We propose that oxidative stress generated by low catalase levels in stromal cells promotes these key physiological functions in the young, steady state thymus; in contrast however, the resulting accumulated oxidative damage ultimately impairs function in the aged thymus.
Age-associated thymic atrophy results in diminished production of new T lymphocytes and a concomitant decrease in responsiveness to new pathogens and vaccines. In addition to loss of thymic size with age, we have shown that critical stromal functions, including tissue-restricted antigen (TRA) expression, are diminished with age. We previously identified deficiency of the hydrogen peroxide quenching enzyme catalase (CAT) in thymic stromal cells as a key cause of thymic atrophy during aging, and established that thymic atrophy can be mitigated by genetic or dietary complementation of catalase antioxidant activity. Here, we find that in addition to maintaining thymic mass with age, long-term increases in catalase activity may mitigate age-associated loss of stromal function. Our preliminary studies indicate that life-long overexpression of catalase in mitochondria of transgenic mice (mCAT Tg) results in increased TRA expression, mitigated acquisition of an aged global gene expression signature, and increased maintenance of cortico-medullary organization in aged mCAT Tg mice relative to non-transgenic littermates.
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