Sjögren's syndrome (SS) is a chronic autoimmune disease caused by immune system disorders. The main clinical manifestations of SS are dry mouth and eyes caused by the destruction of exocrine glands, such as the salivary and lacrimal glands, and systemic manifestations, such as interstitial pneumonia, interstitial nephritis and vasculitis. The pathogenesis of this condition is complex. However, this has not been fully elucidated. Treatment mainly consists of glucocorticoids, disease-modifying antirheumatic drugs and biological agents, which can only control inflammation but not repair the tissue. Therefore, identifying methods to regulate immune disorders and repair damaged tissues is imperative. Cell therapy involves the transplantation of autologous or allogeneic normal or bioengineered cells into the body of a patient to replace damaged cells or achieve a stronger immunomodulatory capacity to cure diseases, mainly including stem cell therapy and immune cell therapy. Cell therapy can reduce inflammation, relieve symptoms and promote tissue repair and regeneration of exocrine glands such as the salivary glands. It has broad application prospects and may become a new treatment strategy for patients with SS. However, there are various challenges in cell preparation, culture, storage and transportation. This article reviews the research status and prospects of cell therapies for SS.

Monitor lizards are acclimatized to a variety of environments. Most of the monitor species are terrestrial, although there are arboreal and semiaquatic monitors. Such accommodation requires unique cellular structure and regulatory devices in various organs, particularly their lungs. This study aimed to report the pulmonary guardians and special regulatory devices that may guard and promote the function of the lungs of the Nile monitor lizards (Varanus niloticus). Specially structured vessels were recorded in the pulmonary tissue involving atypical glomus vessels, vessels with variable wall thickness, and a venule with specialized internal elastic membrane. Moreover, numerous lung resident guardians could be identified including both alveolar and interstitial macrophages, dendritic cells, mast cells, and B- and T-lymphocytes. Pericytes were demonstrated surrounding the capillary endothelium with a characteristic direct hetero-cellular junction with telocytes. Telocytes established a microenvironment through an indirect hetero-cellular junction with the interstitial macrophage, dendritic cells, and pneumocyte type II. Collectively, these data indicate a significant role played by the specially structured vessels and the resident immune cells in guarding the pulmonary tissue of the Nile monitor lizards and promoting its function. Telocytes are suggested to play a key role in angiogenesis and cellular communication to promote the function of the immune cells.

Apart from its role as a digestive and absorptive organ, the gastrointestinal (GI) tract is a vital immune organ that encompasses roughly 70 % of the total immune cells of the body. As such, the physical, chemical and nutrient composition of the diet influences overall GI function, effectively as an immune organ. With the improvement in feed technology, agro-industrial co-products that are high in fibre have been widely used as a feed ingredient in the diets of pigs and poultry. Arabinoxylan (AX) and mannan are the most abundant hemicellulosic polysaccharides present in cereal grain and co-product ingredients used in the livestock industry. When monogastric animals consume diets containing high amounts of AX and mannans, stimulation of GI immune cells may occur. This involves the activation of several cellular and molecular pathways of the immune system and requires a considerable amount of energy and nutrients to be expended by the animal, which may ultimately influence overall health and growth performance of animals. Therefore, a better understanding of the role of AX and mannan in immune modulation will be helpful in modulating untoward GI immune responses, thereby minimising nutrient and energy expenditure toward this effort. This review will summarise pertinent research on the role of oligosaccharides and polysaccharides containing AX and mannans in immune modulation in order to preserve gut integrity.

The present study describes in detail the morphological characteristics of the process of ovarian follicular atresia in Redbelly tilapia (Coptodon zillii) during the nonbreeding season using light and electron microscopy and immunohistochemistry. The follicular regression process was initiated with shrinkage and disintegration of the nuclear membrane of oocytes resulting in dispersing of chromatin within the ooplasm, followed by marked hyperplasia and hypertrophy of follicular and granulosa cells, which exhibited a strong phagocytic activity to engulf the liquefied yolk particles. Rodlet cells and granulocytes were recorded on the follicular wall and invaded the regressed follicles. Rodlet cells expressed a strong immunoreactivity to matrix metalloperoxidase (MMP-9) and α-smooth muscle actin, while neutrophils expressed a strong reactivity to Myeloperoxidase-3 (MPO). In the advanced stage of follicular atresia, the yolk was almost phagocytized and resorbed and the regressed follicle lost its integrity and appeared to be formed of a cellular mass of phagocytic cells. Transmission electron microscopy revealed the presence of neutrophils, eosinophils, and dendritic cells within the atretic follicle in between these phagocytic cells. Moreover, numerous lysosomes, granules, and phagosomes were observed within the cytoplasm of both phagocytic cells and granulocytes. Telocytes were also demonstrated within the highly thickened richly vascularized theca layer during the late stages of follicular atresia. Immunohistochemical staining for caspase-3 established the participation of apoptosis in the advanced stages of follicular regression. Immune cells, rodlet cells, and telocytes in combination with follicular cells play an essential role in follicular atresia. In conclusion, the present study provides a new evidence on the role of both somatic and immune cells in the phenomenon of ovarian follicular atresia in Redbelly tilapia (Coptodon zillii) during the nonbreeding season.

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

Immunomodulation by molecules from Trichinella spiralis (T. spiralis) has been widely reported. Glutathione-S-transferase (GST) is a major immune-modulator of the family of detoxification enzymes. Dendritic cells (DCs) are an important target for the regulation of the immune response by T. spiralis. In this study, the recombinant GST of T. spiralis (rTs-GST) was expressed and purified. rTs-GST induced low CD40 expression and moderate CD80, CD86 and MHC-II expressions and inhibited the increase of CD40, CD80 and CD86 on DCs induced by LPS. We showed that rTs-GST decreased the LPS-induced elevated level of pro-inflammatory cytokines of DCs and enhanced the level of regulatory cytokines IL-10 and TGF-β. Furthermore, co-culture of DCs and CD4+ T cells demonstrated that rTs-GST-treated DCs suppressed the proliferation of OVA-specific CD4+ T cells and increased the population of regulatory T cells (Tregs). rTs-GST-treated DCs induced a higher level of IL-4, IL-10 and TGF-β, but inhibited the level of IFN-γ. This indicates that rTs-GST-pulsed DCs induce both Th2-type responses and Tregs. These findings contribute to the current understanding of the immunomodulation of Ts-GST on cellular response and immunomodulation of T. spiralis.

Early-life nutrition plays a critical role in fetal growth and development. Food intake absence and excess are the two main types of energy malnutrition that predispose to the appearance of diseases in adulthood, according to the hypothesis of ‘developmental origins of health and disease’. Epidemiological data have shown an association between early-life malnutrition and the metabolic syndrome in later life. Evidence has also demonstrated that nutrition during this period of life can affect the development of the immune system through epigenetic mechanisms. Thus, epigenetics has an essential role in the complex interplay between environmental factors and genetics. Altogether, this leads to the inflammatory response that is commonly seen in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. In conjunction, DNA methylation, covalent modification of histones and the expression of non-coding RNA are the epigenetic phenomena that affect inflammatory processes in the context of NAFLD. Here, we highlight current understanding of the mechanisms underlying developmental programming of NAFLD linked to epigenetic modulation of the immune system and environmental factors, such as malnutrition.

Despite the profound health implications of Necator americanus infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs). Our data show that co-culturing DCs and the larvae trigger ex-sheathing of hookworms rapidly where a majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed larvae to migrate away unchallenged. Intriguingly, DCs show negligible interaction with the ex-sheathed larvae, alluding to differences between the surface chemistry of the larva and its sheath. Furthermore, blocking of two key C-type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted in inhibition of ex-sheathing process and DC sequestration, highlighting the importance of C-type lectins on DCs in the induction of the ex-sheathing. Analyses of DC phenotype and cytokine profile after co-culture with the N. americanus larvae showed an immature phenotype as evidenced by the low expression of the maturation markers and cytokines. These data provide new insights into early events at the interface of human DCs and N. americanus larvae and could explain how L3 evade immune recognition upon initial interaction with DCs.

Dendritic cells (DC) are central regulators of immune responses and professional antigen-presenting cells (APCs) with the unique ability to induce both innate immune responses and a highly specific acquired immunity. DC communicates through chemical and mechanical signals in the initiation and maintenance of immune responses. DC forms immunological synapses with T-cells thus pulling T-cells strings and leading to activation of T-cells. Owing to their properties, DC are often called ‘nature's adjuvants’ and thus have become an important component of any vaccination strategy. Coccidiosis is a major intestinal disease caused by Eimeria spp., affecting economically valuable livestock animals such as chickens and turkeys. Economic losses are associated with decreased productivity in afflicted poultry. Vaccination strategies involving DC have been developed owing to the special properties of these cells in coordinating innate and adaptive immune responses. Vaccination of chickens with exosomes isolated from DC containing parasite antigens (Ags) represents a promising alternative strategy to control avian coccidiosis. In recent years, emergence of new chicken DC has opened a new horizon for the development of new vaccines and DC derived vaccine could be a possible strategy to control coccidiosis in field. This review summarises the current state of knowledge of DC and their specific functions in immunity against avian coccidiosis.

Dendritic cells (DCs) are antigen-presenting cells (APCs) with the unique ability to induce both innate immune responses and a highly specific acquired immunity. DCs are crucial to induce immunity, and their maturation and functions are influenced by microbial and environmental stimuli. Chicken DCs are composed of several subtypes including bursal secretory dendritic cells (BSDCs), follicular dendritic cells (FDCs), and thymic dendritic cells (TDCs). DC maturation depends on the nature of the perturbation and permits unique and efficient immune responses for each pathogen. DCs differentially recognise the viruses, bacteria, parasite and fungi and specifically regulate the immune response. Dendritic cells (DCs) are ‘nature's adjuvants’ and, as such represent an essential component of any vaccination strategy. The understanding of DC regulatory mechanisms opens a new horizon for the development of new vaccines and their targeting with the vaccination for elicitation of better immunity levels. The following review summarises the current state of knowledge of DCs and their specific functions during host pathogens interaction.

Bovine viral diarrhea virus (BVDV) has long been associated with a wide variety of clinical syndromes and immune dysregulation, many which result in secondary bacterial infections. Current understanding of immune cell interactions that result in activation and tolerance are explored in light of BVDV infection including: depletion of lymphocytes, effects on neutrophils, natural killer cells, and the role of receptors and cytokines. In addition, we review some new information on the effect of BVDV on immune development in the fetal liver, the role of resident macrophages, and greater implications for persistent infection.

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain more insights into the underlying mechanisms, in the present study, we analysed the modulation of bone marrow-derived dendritic cells (BM-DC) from BALB/c (T helper (Th)2 biased) v. C57BL/6 (Th1 biased) mice. Our findings showed that VSL#3 differed from pure Toll-like receptor (TLR) ligands by inducing the production of various cytokines, including IL-12 p70 subunit (IL-12p70), IL-23 and IL-10. Dedicated TLR arrays were employed to profile mRNA from BM-DC cultured with lipopolysaccharide (LPS), VSL#3, or a combination of both. This approach led to the identification of (1) a cluster of genes that were up- or down-regulated, irrespective of the stimulus, (2) a cluster of genes that were synergistically up-regulated by LPS and VSL#3 in BM-DC from C57BL/6 mice, but not in those from BALB/c mice, and (3) a cluster of LPS-induced genes that were suppressed by VSL#3, in particular chemokine genes. These data show that this probiotic mixture has both pro- and anti-inflammatory effects on BM-DC and suggest that their immune-modulating properties in vivo may depend on the genetic background of the host.

To investigate the frequencies of dendritic cells (DCs) and Toll-like receptor 3 (TLR3) in neonates of HBsAg-positive mothers with different HBV serological profiles, we conducted a study in Taiyuan, China. The study included 144 HBsAg-positive mothers and their neonates. The frequencies of DCs and TLR3 were determined using four-colour flow-cytometric analysis. DC and TLR3 frequencies were not related to HBV intrauterine transmission, maternal HBeAg positivity, maternal HBV DNA positivity and HBeAg/HBV DNA double-positivity. The plasmacytoid dendritic cell (pDC) frequencies in neonates whose maternal HBV DNA was >5 × 107 copies/ml decreased significantly compared to that in neonates whose maternal HBV DNA was ⩽5 × 107 copies/ml (Z = − 2·170, P = 0·03) or whose maternal HBV DNA was negative (Z = − 1·981 P = 0·048). This study suggests that neonatal pDC frequencies decrease when maternal HBV DNA loads are >5 × 107 copies/ml.

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance to the commensal microbiota and food antigens. Different strains of probiotics possess the ability to finely regulate the activation of dendritic cells (DC), polarising the subsequent activity of T-cells. Nevertheless, information about their underlying mechanisms of action is scarce. In the present study, we investigated the immunomodulatory effects of a potentially probiotic strain, Lactobacillus rhamnosus CNCM I-4036, and its cell-free culture supernatant (CFS) on human DC challenged with Escherichia coli. The results showed that the levels of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8 and IL-12p70 were higher in the cells treated with live L. rhamnosus than in the cells treated with the CFS. In the presence of E. coli, the supernatant was more effective than the probiotic bacteria in reducing the secretion of pro-inflammatory cytokines. In addition, live L. rhamnosus potently induced the production of transforming growth factor (TGF)-β1 and TGF-β2, whereas the CFS increased the secretion of TGF-β1. However, in the presence of E. coli, both treatments restored the levels of TGF-β. The probiotic strain L. rhamnosus CNCM I-4036 and its CFS were able to activate the Toll-like receptor signalling pathway, enhancing innate immunity. The two treatments induced gene transcription of TLR-9. Live L. rhamnosus activated the expression of TLR-2 and TLR-4 genes, whereas the CFS increased the expression of TLR-1 and TLR-5 genes. In response to the stimulation with probiotic/CFS and E. coli, the expression of each gene tested was notably increased, with the exception of TNF-α and NFKBIA. In conclusion, the CFS exhibited an extraordinary ability to suppress the production of pro-inflammatory cytokines by DC, and may be used as an effective and safer alternative to live bacteria.

Commensal bacteria are important in intestinal homeostasis and appear to play a role in early tolerance to foreign antigens. The requirement for homeostatic balance between tolerance and immunity poses a unique regulatory challenge to mucosal immune systems. Dysregulation of this balance can contribute to the pathogenesis of numerous inflammatory conditions such as inflammatory bowel diseases. The primary response to these bacteria is triggered by pattern recognition receptors (PRR), which bind pathogen-associated molecular patterns (PAMP). PRR comprise Toll-like receptors (TLR), nucleotide-binding oligomerization domains, adhesion molecules and lectins. Probiotics are living commensal micro-organisms of the intestinal tract with clinically documented health effects in human subjects. They are known to affect the gastrointestinal tract and the associated immune system and to have numerous effects on intestinal function and immune responses, including immunotolerance. This last effect appears to be mediated via regulatory T-cell activation by intestinal dendritic cells and the low activation of T-helper 1 and 2 (Th1 and Th2) cell inflammatory responses. However, the precise mechanisms of probiotic activity remain poorly understood. The aim of the present work was to review the function of TLR in the development of immunotolerance and examine the specific role of probiotics in the regulation of tolerance to antigens.

Prebiotics may increase Zn absorption, a mineral known to play a central role in the immune system. Zn-deficient states are characterised by suppressed immune function, while prebiotics may improve both gut and cell-mediated immunity. Our objective was to determine if inulin alters the number and proportion of immune cells in the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP), ex vivo cytokine secretion, intestinal permeability and Zn status in healthy as well as Zn-deficient rats. Weanling female rats were fed diets supplemented with 5 % cellulose (CEL) or 5 % inulin (PRE) for 4 weeks. The rats received the CEL or PRE diet ad libitum (ZN) or in restricted amounts (DR), or deficient in Zn (ZD) for another 4 weeks. The PRE-fed rats had a higher number and proportion of dendritic cells in PP, and greater ex vivo secretion of IL-2, IL-10 and interferon-γ from spleen and MLN cells compared with CEL-fed rats. PRE reduced the number and proportion of T cell receptor (TCR)-αβ+CD8+ cells in spleen and CD45RA+ cells in MLN compared with CEL. ZD rats had lower serum IgG2a and T cell numbers in MLN compared with ZN and DR rats. TCRγδ+ cell numbers in PP were higher in ZD-PRE rats compared with ZD-CEL rats. Femur Zn concentrations of DR-PRE rats were higher than those of DR-CEL rats. Intestinal permeability was unchanged. The higher proportion and number of dendritic cells in the PP of inulin-fed rats indicates a need for further research on how prebiotics and their metabolites affect immune function possibly through intestinal dendritic cells.

Breast-feeding is the predominant postnatal transmission route for HIV-1 infection in children. However, a majority of breast-fed infants do not become HIV-infected despite continuous exposure to the virus through their mothers' milk over many months. What protects some breast-fed infants from HIV-1 infection? HIV-1 entry across the infant's mucosal barrier is partially mediated through binding of the HIV-1 surface glycoprotein gp120 to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) on human dendritic cells. Lewis antigen glycans, present in human milk, bind to DC-SIGN and inhibit HIV-1 transfer to CD4+T lymphocytes. Human milk contains a high amount of unbound, complex oligosaccharides (5–10 g/l) that carry one or more Lewis antigen glycans, and we hypothesized that they compete with gp120 for DC-SIGN binding. Here, we show in two independent assays that physiological concentrations of human milk oligosaccharides significantly reduce gp120 binding to DC-SIGN by more than 80 %. These results may provide an additional explanation for the inhibitory effects of human milk on HIV-1 mother-to-child-transmission. Identifying the specific milk oligosaccharides that interact with DC-SIGN may guide the development of glycan-based drugs that prevent transmission of HIV-1 and other pathogens that use DC-SIGN as an entry point. However, blocking DC-SIGN may be a two-edged sword.

Dendritic cells are central to the initiation of primary immune responses. They are the only antigen-presenting cell capable of stimulating naive T cells, and hence they are pivotal in the generation of adaptive immunity. Dendritic cells also interact with and influence the response of cells of the innate immune system. The manner in which dendritic cells influence the responses in cells of both the innate and adaptive immune systems has consequences for the bias of the adaptive response that mediates immunity to infection after vaccination or infection. It also provides an opportunity to intervene and to influence the response, allowing ways of developing appropriate vaccination strategies. Mouse and human studies have identified myeloid, lymphoid and plasmacytoid dendritic cells. Studies in domesticated animals with agents of specific infectious diseases have confirmed the applicability of certain of the generic models developed from mice or from in vitro studies on human cells. In vivo and ex vivo studies in cattle have demonstrated the existence of a number of subpopulations of myeloid dendritic cells. These cells differ in their ability to stimulate T cells and in the cytokines that they produce, observations clearly having important implications for the bias of the T-cell response. Dendritic cells also interact with the innate immune system, inducing responses that potentially bias the subsequent adaptive response.

Dendritic cells have been shown to be the main antigen-presenting cells in vitro and in vivo, playing a pivotal role in the induction of both tolerance and immunity. Dendritic cells from humans and mice have been extensively studied and dendritic cell-based vaccines have been shown to be effective in the prevention and treatment of infectious, allergic and neoplastic diseases. Studies of dendritic cells of domestic animal origin are becoming available and confirm a role for these cells in the pathogenesis of a variety of animal diseases, suggesting that dendritic cells could be used as adjuvants for prophylactic and therapeutic strategies in veterinary medicine.