For many years, the central nervous system and the immune system were considered two autonomous entities. However, extensive research in the field of neuroimmunomodulation during the past decades has ...demonstrated the presence of different neuropeptides and their respective receptors in the immune cells. More importantly, it has provided evidence for the direct effects of neuropeptides on the immune cell functions. Neuropeptide Y (NPY) is generally considered the most abundant peptide in the central and peripheral nervous system. However, it is also distinguished by exhibiting pleiotropic functions in many other physiological systems, including the immune system. NPY affects the functions of the cells of the adaptive and innate immunity. In this respect, NPY is known to modulate immune cell trafficking, T helper cell differentiation, cytokine secretion, natural killer cell activity, phagocytosis and the production of reactive oxygen species. The specific Y receptors have been found in immune cells, and their expression is amplified upon immune stimulation. Different Y receptor subtypes may mediate an opposite effect of NPY on the particular function, thus underlining its regulatory role. Since the immune cells are capable of producing NPY upon appropriate stimulation, this peptide can regulate immune cell functions in an autocrine/paracrine manner. NPY also has important implications in several immune-mediated disorders, which affirms the clear need for further investigation of its role in either the mechanisms of the disease development or its possible therapeutic capacity. This review summarises the key points of NPY’s mission throughout the immune system.
Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, ...innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS,
T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.
Complete Freund's adjuvant (CFA) is used as a standard adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model in multiple sclerosis ...studies. Still, CFA induces glial activation and neuroinflammation on its own and provokes pain. In addition, as CFA contains Mycobacteria, an immune response against bacterial antigens is induced in parallel to the response against central nervous system antigens. Thus, CFA can be considered as a confounding factor in multiple sclerosis-related studies performed on EAE. Here, we discuss the effects of CFA in EAE in detail and present EAE variants induced in experimental animals without the use of CFA. We put forward CFA-free EAE variants as valuable tools for studying multiple sclerosis pathogenesis and therapeutic approaches.
The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) ...model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.
Ethyl pyruvate (EP) is a redox-active compound that has been previously shown to be effective in restraining immune hyperactivity in animal models of various autoimmune and chronic inflammatory ...diseases. Importantly, EP has also been proven to have a potent tolerogenic effect on dendritic cells (DCs). Here, the influence of EP on the signaling pathways in DCs relevant for their tolerogenicity, including anti-inflammatory NRF2 and pro-inflammatory NF-κB, was explored. Specifically, the effects of EP on DCs obtained by GM-CSF-directed differentiation of murine bone marrow precursor cells and matured under the influence of lipopolysaccharide (LPS) were examined via immunocytochemistry and RT-PCR. EP counteracted LPS-imposed morphological changes and down-regulated the LPS-induced expression of pro-inflammatory mediators in DCs. While it reduced the activation of NF-κB, EP potentiated NRF2 and downstream antioxidative molecules, thus implying the regulation of NRF2 signaling pathways as the major reason for the tolerizing effects of EP on DCs.
This study assessed the effects of season on health, behaviour, physiological stress parameters, and carcass and meat quality in a total of 480 slaughter pigs. The following health indicators were ...recorded: pneumonia, pleurisy, milk spots, and pericarditis. Behaviour was monitored during unloading (slipping, falling, turning back, reluctance to move, panting, shivering) and lairaging (panting, shivering, huddling). Blood lactate and glucose concentrations were determined at exsanguination. Performance indices (live weight, daily weight gain), carcass (carcass weight, backfat and loin thickness, lean meat content, carcass lesion score), and meat quality (pH, temperature, drip, thawing and cooking losses, colour, marbling) traits were measured postmortem. Pigs slaughtered in winter had the highest live weight, carcass weight, loin thickness, and carcass lesion score, while the lowest live weight, carcass weight, and backfat thickness were recorded in pigs slaughtered in summer. The highest lactate and glucose concentrations were recorded in pigs slaughtered in summer. The highest prevalence of red, soft, and exudative meat was recorded in pigs slaughtered in winter. Pigs slaughtered in summer had the lowest pH, the highest thawing loss, L* value, b* value, and occurrence of pale, soft, and exudative meat. Pigs slaughtered in autumn had the lowest drip loss, cooking loss, L* value, b* value, and the greatest percentage of red, firm, and nonexudative meat. In conclusion, the summer and winter temperatures compromised health and welfare and reduced carcass and meat quality in slaughter pigs, indicating that protection against heat and cold stress is not yet effective.
The fatty acid (FA) profiles of lamb muscle and adipose tissue originating from ten different grazing areas in North Macedonia and an assessment of whether the meat origin could be distinguished on ...the basis of FA profile are presented. Muscle and adipose tissues of three-month-old male lambs (crossbreds of autochthonous Ovcepolian and Württemberg) reared on spring pastures were studied. Statistically significant differences in the individual FA contents, FA groups and FA ratios were observed between lamb tissues from the different geographic regions. Canonical discriminant analysis showed there was a significant linear divergence between tissues from almost all examined regions. The greatest weight in the differentiation of the different areas showed fatty acid ratios, C18:3n3, C18:1n9c and C20:5n3 for the muscle tissue, as well as C18:1n9c, C18:2n6c, C16:1 and C17:1 for the adipose tissue. This showed that the FA composition of muscle and adipose tissue obtained from lambs reared on pasture could serve as a useful indicator to aid differentiation of its geographic origin but it should be confirmed through further replicated studies.
•Fatty acid profiles of lambs from ten grazing areas in North Macedonia were investigated.•Significant difference in the FA profilesbetweengeographic regions was observed.•Canonical discriminant analysis of FA's showed a linear divergence between regions.•FA profile of lambs reared on pasture could serve to distinguishdifferent grazing areas.
Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental ...autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto)reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.
The goal of this study conducted in Serbia was to detect HEV in pig liver samples from slaughterhouses, retail outlets, and environmental swabs over the course of a year. All positive HEV samples ...were measured and expressed as HEV gene copy numbers per gram of sample, and a representative number of samples were sequenced using the Sanger approach. A total of 45 HEV-positive samples were re-amplified using nested RT-PCR employing CODEHOP primers targeting ORF2 (493 nucleotides). The average prevalence of the HEV genotype 3 in all pig liver samples from the slaughterhouses was 29%, while HEV prevalence was 44% in liver samples from animals younger than 3 months. HEV RNA was found in thirteen out of sixty (22%) environmental swab samples that were taken from different surfaces along the slaughter line. Our findings confirmed seasonal patterns in HEV prevalence, with two picks (summer and winter periods) during the one-year examination. Among HEV-positive samples, the average viral particles for all positive liver samples was 4.41 ± 1.69 log
genome copies per gram. Phylogenetic analysis revealed the majority of HEV strains (43/45) from Serbia were grouped in the HEV-3a subtype, while two strains were classified into the HEV-3c subtype, and one strain could not be classified into any of the HEV-3 subtypes.
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