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It has been well-established that age-associated low-grade chronic inflammation contributes to the development of a spectrum of chronic diseases, including diabetes mellitus, ischemic heart disease, stroke, cancer, chronic kidney disease, non-alcoholic fatty liver disease and neurodegenerative diseases, which affect the quality of life of the elderly and influence their life span. This phenomenon is suggested to arise due to the weakening of the regulatory mechanisms of the immune response, and the persistence of exogenous and endogenous (reflecting oxidative cell injury) antigenic challenges, so it is referred to as oxi-inflamm-aging. Considering that the development of age-associated chronic inflammation is "silent", i.e., without clinical signs until the aforementioned complications become apparent, it is important to identify the biomarker(s) or pattern/cluster of biomarkers for this inflammation. It is also important to define new strategies to combat the "silent" damage induced by chronic inflammation. Given that at present there are no reliable biomarkers for chronic inflammation, this review points out the problems in defining biomarker(s) or patterns/clusters of biomarkers for chronic inflammation in order to stimulate further research and points to some possible routes of investigation.

Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine. [ABSTRACT FROM AUTHOR]

The study was aimed to define the putative role of ovarian hormones in shaping thymocyte apoptosis and proliferation during thymic involution. Thymocytes from young adult and middle-aged rats ovariectomized (Ox) before puberty were examined for apoptosis and proliferation. Apoptosis and proliferation were measured in fresh thymocyte suspensions and in their 18-hour cultures, and fresh thymocyte suspensions, respectively. The thymocyte population and the major thymocyte subsets were analyzed following triple staining using anti-CD4 and anti-CD8 monoclonal antibodies and 7-AAD to label apoptotic or proliferating cells. The frequency of apoptotic cells was lower in thymocyte suspensions and cultures from Ox rats of both ages. This reflected in a diminished frequency of apoptotic cells amongst CD4+CD8+ double positive (DP) and CD4+CD8- single positive (SP), and DP cells in young and middle-aged Ox rats, respectively. Additionally, in thymocyte cultures from Ox rats the frequency of apoptotic cells amongst CD4+CD8- and CD4-CD8+ SP cells decreased with age, but increased within DP and CD4-CD8- double negative (DN) subsets, reaching in the former subset from middle-aged Ox rats higher values than in age-matched controls. The frequency of proliferating cells was also lower in Ox rats than in controls. This reflected the lower frequency of cycling cells amongst CD4+CD8- SP and CD4-CD8+ SP thymocytes in young rats, and DP and CD4-CD8+ SP thymocytes in middle-aged rats. Besides, in both SP and DP thymocyte subsets from Ox rats the frequency of proliferating cells declined with age. In conclusion, thymocyte apoptosis and proliferation exhibit ovarian hormone-dependent thymocyte subset specific alterations during thymic involution. [Projekat Ministarstva nauke Republike Srbije, br. 175050]

The study was designed to explore the expression of different neuropeptides, viz. vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), bombesin and motilin in the cells of fetal and adult human thymus. Immunohistochemical staining revealed that cortical and medullary thymocytes were labeled by all antibodies, except those specific for motilin. Immunoreactive VIP and SP were observed in the solitary epithelial cells located in the subcapsular/subtrabecular cortex, at the corticomedullary junction and in the medulla. The cells within the subcapsular/subtrabecular monolayer, rare solitary cells in the deep cortex and epithelial cell network in the medulla, were labeled with antibodies to CGRP and bombesin. Hassall’s corpuscles were labeled with all antibodies except that specific for SP. The obtained data obtained testify to the expression of different neuropeptides in human thymic lymphoid and non-lymphoid cells and suggest a role for neuroendocrine hormone-mediated mechanisms in the regulation of thymic homeostasis in humans.

Introduction: Considering significance of mechanisms of central tolerance for development of autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), and suppressive influence of circulating proinflammatory cytokines and alterations in brain-thymus communication, characteristic for the central nervous system (CNS) autoimmune diseases, on thymopoiesis, the study interogated putative strain-based thymus-related specificities relevant for the opposite effects of ageing on susceptibility of Dark Agouti (DA) and Albino Oxford (AO) rats to EAE. Methods: Quantitative and qualitative changes in thymopoiesis including underlying mechanisms were examined using flow cytometry and RT-qPCR quantification of mRNAs for molecules relevant for integrity of stroma and T-cell development, respectively. Results: With ageing, differently from DA rats, in AO rats the surface density of CD90, a negative regulator of selection threshold, on thymocytes undergoing lineage commitment was upregulated (consistent with TGF-β expression downregulation), whereas the generation of natural CD4+CD25+Foxp3+ regulatory T cells (nTregs) was impaired reflecting differences in thymic expression of cytokines supporting their development. Additionally, specifically in old AO rats, in whom EAE development depends on IL-17-producing CD8+ T cells, their thymic differentiation was augmented, reflecting augmented thymic IL-4 expression. In turn, differently from old DA rats developing self-limiting EAE, in age-matched AO rats developing EAE of prolonged duration, EAE development led to impaired generation of nTregs and accumulation of proinflammatory, cytotoxic CD28–CD4+ T cells in the periphery. Discussion: The study indicates that strain differences in age-related changes in the efficacy of central tolerance, in addition to enhanced thymic generation of CD8+ T cells prone to differentiate into IL-17-producing cells, could partly explain the opposite effect of ageing on DA and AO rat susceptibility to EAE induction. Additionally, it suggested that EAE development leading to a less efficient thymic output of CD4+ cells and nTregs in old AO rats than their DA counterparts could contribute to prolonged EAE duration in AO compared with DA rats. Conclusion: The study warns to caution when designing therapeutic interventions to enhance thymic activity in genetically diverse populations, e.g., humans, and interpreting their outcomes. Furthermore, it indicates that CNS autoimmune pathology may additionally worsen thymic involution and age-related immune changes. [ABSTRACT FROM AUTHOR]