Immune Disturbances Research Articles

Hypervolemia-Induced Immune Disturbances Do Not Involve IL-1ß but IL-6 and IL-10 Activation in Haemodialysis Patients.

Dysregulated fluid homeostasis is frequent in haemodialysis (HD) patients and is linked to inflammation which may be elicited by endotoxemia. The impact of hypervolemia on immune cells has not been studied in detail. Therefore, we analysed the hypervolemic activation of peripheral blood mononuclear cells (PBMCs) in HD with special focus on the NLRP3 inflammasome response. First, 45 HD were included in the observational study. Immune parameters including cell counts, caspase-1, oxidative stress, cytokine gene expression and serum analysis (IL-1ß, IL-6, IL-10) were all measured at two time points. Fluid status was evaluated by electrical bioimpedance vector analysis, defining hypervolemia (H) as >75 vector percentile. Then, 17 patients were classified as hypervolemic (H-HD), 19 as normovolemic (N-HD) and 9 failed to meet the inclusion criteria. Monocytes were elevated and lymphocytes were decreased by hypervolemia. NLRP3 inflammasome components, caspase-1 and IL-1ß expression were not statistically different between the two groups. Serum IL-6 levels were significantly elevated in H-HD. IL-10 mRNA transcripts were elevated by 2-fold in H-HD but were not efficiently translated. We conclude that the NLRP3 inflammasome is not activated by hypervolemia thus refuting the thesis that endotoxemia may be a main driver for inflammation in H-HD. Nevertheless, inflammation is generally higher in H-HD compared to N-HD patients and is not sufficiently balanced by anti-inflammatory mechanisms.

Alergia e intolerancia a antiinflamatorios no esteroideos en pediatría Comité Nacional de Alergia

Nonsteroidal anti-inflammatory drugs are widely prescribed in children. They are the second cause of drug's reactions in pediatrics after beta-lactam antibiotics, however only a part of them are hypersensitivity reactions. The prevalence of these reactions to nonsteroidal anti-inflammatory drugs in children is 0.3 %, increasing to 5 % in asthmatics. The different physiopathological mechanisms involved (inhibition of cyclooxygenase, immunoglobulin E-mediated hypersensitivity, reactive T lymphocytes and/or disturbance of innate immunity) will cause different clinical entities with diverse symptoms. The confusion between the common symptoms of a viral infection and a hypersensitivity reaction, and the variability of the clinical presentations make diagnosis a real challenge. A detailed clinical history, laboratory, skin and controlled provocation tests will provide strategies for each patient, without labeling a child who is not an allergic one, or taking unnecessary risks with those who are sensitized.

Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure

BackgroundEvidence suggests that cytokine imbalances may be at the root of deficits that occur in numerous neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Notably, while clinical studies have demonstrated maternal cytokine imbalances with alcohol consumption during pregnancy—and data from animal models have identified immune disturbances in alcohol-exposed offspring—to date, immune alterations in alcohol-exposed children have not been explored. Thus, here we hypothesized that perturbations in the immune environment as a result of prenatal alcohol exposure will program the developing immune system, and result in immune dysfunction into childhood. Due to the important role of cytokines in brain development/function, we further hypothesized that child immune profiles might be associated with their neurodevelopmental status.MethodsAs part of a longitudinal study in Ukraine, children of mothers reporting low/no alcohol consumption or moderate-to-heavy alcohol consumption during pregnancy were enrolled in the study and received neurodevelopmental assessments. Group stratification was based on maternal alcohol consumption and child neurodevelopmental status resulting in the following groups: A/TD, alcohol-consuming mother, typically developing child; A/ND, alcohol-consuming mother, neurodevelopmental delay in the child; C/TD, control mother (low/no alcohol consumption), typically development child; and C/ND, control mother, neurodevelopmental delay in the child. Forty cytokines/chemokines were measured in plasma and data were analyzed using regression and constrained principle component analysis.ResultsAnalyses revealed differential cytokine network activity associated with both prenatal alcohol exposure and neurodevelopmental status. Specifically, alcohol-exposed children showed activation of a cytokine network including eotaxin-3, eotaxin, and bFGF, irrespective of neurodevelopmental status. However, another cytokine network was differentially activated based on neurodevelopmental outcome: A/TD showed activation of MIP-1β, MDC, and MCP-4, and inhibition of CRP and PlGF, with opposing pattern of activation/inhibition detected in the A/ND group. By contrast, in the absence of alcohol-exposure, activation of a network including IL-2, TNF-β, IL-10, and IL-15 was associated with neurodevelopmental delay.ConclusionsTaken together, this comprehensive assessment of immune markers allowed for the identification of unique immune milieus that are associated with alcohol exposure as well as both alcohol-related and alcohol-independent neurodevelopmental delay. These findings are a critical step towards establishing unique immune biomarkers for alcohol-related and alcohol-independent neurodevelopmental delay.

High activation and skewed T cell differentiation are associated with low IL-17A levels in a hu-PBL-NSG-SGM3 mouse model of HIV infection.

The humanized NOD/SCID/IL-2 receptor γ-chainnull (NSG) mouse model has been widely used for the study of HIV pathogenesis. Here, NSG mice with transgenic expression of human stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 (NSG-SGM3) were injected with peripheral blood leukocytes (PBL mice) from two HIV-infected (HIV+ ) patients who were under anti-retroviral therapy (ART; referred as HIV+ mice) or one HIV-seronegative healthy volunteer (HIV- ). Such mice are either hu-PBL-NSG-SGM3 HIV+ or HIV- mice, depending on the source of PBL. The kinetics of HIV replication and T cell responses following engraftment were evaluated in peripheral blood and secondary lymphoid tissues. High HIV replication and low CD4:CD8 ratios were observed in HIV+ mice in the absence of anti-retroviral therapy (ART). Consistent with high activation and skewed differentiation of T cells from the HIV-infected donor, HIV+ mice exhibited a higher T cell co-expression of human leukocyte antigen D-related (HLA-DR) and CD38 than HIV- mice, as well as a shifted differentiation to a CCR7- CD45RA+ terminal effector profile, even in the presence of ART. In addition, HIV replication and the activation/differentiation disturbances of T cells were associated with decreased plasma levels of IL-17A. Thus, this hu-PBL-NSG-SGM3 mouse model recapitulates some immune disturbances occurring in HIV-infected patients, underlying its potential use for studying pathogenic events during this infection.

In the Back Drop of Overuse of Synthetic Drugs, can Botanicals be One of the Answers: A Pilot Study on the Medicinal Use of Chlorophytum and Curcuma by Tribals of Central India

Background: In several recent surveys, it has been found that more people suffer because of over and indiscriminate use of synthetic drugs, chemicals and antibiotics, particularly with regard to issues like drug sensitivity, resistance, immune disturbances, and economic burdens, ultimately leading to a weak prognosis of a large number of diseases, eventually defeating the purpose of medicinal efficacy. We propose the old age use of scientifically validated natural compounds of plants and their products for a strong immune system along with a successful treatment regimen which can be effective as well as safe without side effects. Objective: The aim of the present work is to evaluate the various medicinal uses and applicability of Chlorophytum borivilianum, Chlorophytum tuberosum and Curcuma longa as natural plant-based ingredients by tribal communities. Methods: A survey was carried on the rural folks who used natural botanicals for alleviating their several common disorders successfully. Chlorophytum species of Liliaceae and Curcuma of Zingiberaceae are traditional rare Indian medicinal herbs widely used in the indigenous system of medicine since ancient time. A total number of 196 individuals were interviewed which included both men and women, in which the main objective was to explore the different forms of these medicinal plant species used with water or with milk by tribal folk for their wide range of common ailments such as pain in joints, loss of appetite, cold, sore throat, fever and general weakness. Results: The tribal people were found to use these plants for many of their problems such as physical weakness, natal and postnatal problems, lactation problems, cold and fever, sore throat, inflammation, joint pain, etc. Many of them (60-80%) were able to overcome their varied health problems to a great extent such as inflammation (69.4%), joint pain and arthritis (66.6%), sore throat and cold (87.5%), physical weakness (66%), natal and postnatal problems (75%). Conclusion: The findings strongly support the use of natural compounds for a safe and effective means of treating loss of appetite, general weakness, pain of the joints, inflammation and other related ailments by the people of tribal areas of Border States of MP and Maharashtra, having little access to modern health care facilities.

Diagnosis and natural history of preclinical and early inflammatory bowel disease.

Inflammatory bowel disease is a chronic and progressive disorder of the gastrointestinal tract. A relevant proportion of patients develop complicated lesions, defined as strictures, fistulas and/or abscesses already at diagnosis, and this proportion increases over time. The preclinical phase defines the period of time from the appearance of the first immune disturbances until the development of overt disease, and it may be present months to years before the diagnosis. Multiple biomarkers (e.g., C-reactive protein, interleukin-6, fecal calprotectin) and cellular mechanisms (e.g., complement cascade, lysosomes, innate immunity, and glycosaminoglycan metabolism) are already altered during this period. Research in this area allows the description of the initial immune disturbances that may identify potential targets and lead to the development of new drug therapies. During this period, different interventions in high-risk individuals, including drugs or environmental factors, will open the possibility of innovative strategies focused on the reduction of complications, or even prevention trials for inflammatory bowel disease. Here, we review the most relevant findings regarding the characteristics, prevalence and biomarkers associated with preclinical disease, along with their possible use in our future clinical practice.

Alterations of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis.

BackgroundEndometriosis is a chronic inflammatory disorder with known immune disturbances. The aim of this study was to compare the frequency of different CD4+ T cells [T helper (Th)1, Th2, Th17 and regulatory T cells (Tregs)] in peripheral blood (PB) and peritoneal fluid (PF) of patients that have early and advanced stages of endome- triosis with a control group.Materials and MethodsIn this case control study, PB and PF samples were collected from women aged 24-40 years who underwent laparoscopy procedures. The frequency of CD4+ T subsets were analysed by flow cytometry and com- pared between three study groups; early endometriosis (stage I, II), advanced endometriosis (stage III, IV) and control (no endometriosis). T cell numbers were compared between the PB and PF in each of the aforementioned groups.ResultsNo statistically significant difference was found between the study groups regarding the numbers of Th1, Th2 and Th17 cells in PB. The PF of patients with advanced endometriosis had increased numbers of Th17 cells compared to the control group (P=0.003), with P values of 0.059 and 0.045 in both menstrual phases. Increased numbers of Th2 cells in PF from early compared to advanced stages of endometriosis were detected exclusively in the luteal phase (P=0.035). The control group had increased numbers of Treg and Th2 cells in the PF compared to PB (both, P value=0.046). However, in the early stages of endometriosis there were more Th2, Th17 and Treg cells in the PF compared to PB (P values: 0.005, 0.047 and 0.013, respectively), while the number of Th17 cells was higher in the PF compared with PB in the advanced stages of endometriosis (P= 0.013).ConclusionThere were increased numbers of Th17 cells in the PF of patients with advanced stages of endometriosis, which could be related to the severity of this disease.

The effect of oleozone gel vs triamcinolone acetonide in ora base on the treatment of erosive/atrophic lichen planus in medically compromised patients

Background Oral lichen planus (OLP) is a common T–cell mediated chronic inflammatory disease, with unknown etiology. One of the etiological factors is involvement of some systemic diseases such as liver disease, diabetes mellitus, and hypertension. The immune system disturbances and oxidative stress may play a role in its pathogenesis. Corticosteroids are the mainstay for treatment of OLP and have its side effects. Oleozone gel was another suggested medication used to treat OLP. Aim The aim was to evaluate the beneficial effect of oleozone gel in the treatment of atrophic/erosive lichen planus in medically compromised patients and to compare it with the effect of triamcinolone acetonide in ora-base as a gold standard treatment. Materials and methods Twenty patients with symptomatic atrophic/erosive OLP were medically compromised and randomly assigned for treatment with 0.1% triamcinolone acetonide gel (group 1) or oleozone gel (group 2). The pain score (visual analog scale) and tumor necrosis factor-α were assessed at baseline (before treatment), 1 month and 3 months. Results Showed nonsignificant differences between the two treatment groups in reducing visual analog scale score and tumor necrosis factor-α value. Conclusion The study revealed that oleozone gel was found to be effective as triamcinolone acetonide in ora-base (0.1%) gel in the treatment of atrophic/erosive OLP in medically compromised patients.

THE EFFECT OF THYMOSIN β4 ON THE FUNCTIONAL ACTIVITY OF THE IMMUNE AND NERVOUS SYSTEM COMPONENTS

The data on properties of thymosin β4, a conserved multifunctional polypeptide of mammals is summarized. Attention has been focused on regulatory activity of thymosin β4 in regard to immune and nervous system components. In these systems thymosin β4 is present in different cell types both stationary and mobile ones. Besides intracellular localization thymosin β4 is also located in extracellular fluids. Inside cells, thymosin β4 has been postulated to regulate actin polymerization as a G-actin-sequestering molecule. But molecular mechanisms of thymosin β4 located extra cells on cell functions remain unclear. The structural-functional organization of thymosin β4 is also discussed. Thymosin β4 is a perspective medicine preparation for the therapy of diseases related to immune and neurological disturbances in patients.

Kynurenine pathway and human systems.

The essential amino acid L-tryptophan (Trp) appears to play an important role in aging by acting as a general regulator of protein homeostasis. The major route of Trp degradation, the kynurenine pathway (KP), produces a range of biologically active metabolites that can impact or be impacted by a variety of body systems, including the endocrine, haemopoietic, immune, intermediary metabolism and neuronal systems, with the end product of the KP, NAD+, being essential for vital cellular processes. An account of the pathway, its regulation and functions is presented in relation to body systems with a summary of previous studies of the impact of aging on the pathway enzymes and metabolites. A low-grade inflammatory environment characterized by elevation of cytokines and other immune modulators and consequent disturbances in KP activity develops with aging. The multifactorial nature of the aging process necessitates assessment of factors determining the progression of this mild dysfunction to age-related diseases and developing strategies aimed at arresting and reversing this progression.

An Increasing Role of Polyphenols as Novel Therapeutics for Alzheimer's: A Review.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with approximately 29 million older people suffering from this disease worldwide. This number is expected to become triple by 2050. AD is a complex and multifactorial neurodegenerative condition, characterized by complex pathology including oxidative stress, formation of aggregates of amyloid and tau, enhanced immune responses, metal deposition and disturbances in cholinesterase enzymes. There is no effective pharmacological treatment for combating the disease to date. The ineffectiveness of current pharmacological interventions in AD has led scientists to search for more safe and effective alternative therapeutic agents. Thus, natural products have become an important avenue for drug discovery in AD research. In this regard, polyphenols are natural products that have been shown to be effective in the modulation of the type of neurodegenerative changes seen in AD, suggesting a possible therapeutic role. The present review focuses on the chemistry of polyphenols, clinical studies for evaluating polyphenols as effective alternatives in AD treatment, cellular and molecular aspects of polyphenols in improving cognitive deficits and the current challenges and futuristic approaches to use polyphenols as safe and effective therapeutic agents in AD treatment.

LOCAL IMMUNITY STATUS OF OROPHARYNX IN PATIENTS WITH SCLEROMA

Scleroma is a rare chronic granulomatous disease of the upper respiratory tract caused by Klebsiella pneumoniae subsp. rhinoscleromatis. To date its pathogenesis is as yet little understood. At the same time, scleroma is associated with a number of immune system disturbances. The aim: To study local immunity status of oropharynx in patients with scleroma, and to compare its parameters in various clinical forms of the disease. 20 apparently healthy subjects and 92 patients with scleroma (33 males, 59 females) underwent clinical immunologic evaluation. There were 31 patients with dominating infiltrative form of scleroma, 30 – with dominating atrophic form, 31 – with dominating scarring form. Concentration of secretory and monomeric immunoglobulin A, immunoglobulin G, α-interferon, interleukin 1β in oropharyngeal secretion was determined by enzyme immunoassay. Patients with scleroma were found to have altered local immunity of oropharyngeal secretion. There was a strong tendency for decreased concentration of secretory immunoglobulin A - 1.3-2.0 times, and decreased immunoglobulin G level – 1.5-2.3 times (р < 0.05) as compared to the values in healthy subjects. Specific features of local immunity in oropharyngeal secretion in various forms of scleromatous inflammatory process in upper respiratory tract were found: the most significant decrease of α-interferon concentration in atrophic and scarring forms of the disease, and the largest increase of anti-inflammatory interleukin 1β and immune complex concentration in infiltrative form of scleroma. The study revealed deficiency of local immunity factors in oropharynx, being indicative of immunopathogenetic role of diagnosed disturbances in development and persistence of chronic inflammation in scleroma, and emphasizing the necessity of immunocorrection in complex therapy of the disease.

Functional Dyspepsia in the Elderly.

Functional dyspepsia is a common condition, and the condition is defined by symptoms using Rome IV criteria. This review addresses the issue of functional dyspepsia in elderly patients, epidemiology, investigation, and treatment. Recent studies show that while the prevalence of dyspepsia declines in the elderly, it is still prevalant investigations to confirm the diagnosis (including mandatory upper gastrointestinal endoscopy) must exclude organic disease. These include ulcers (particularly associated with nonsteroidal antiinflammatory drugs), Helicobacter pylori pathologies, cancer, coeliac disease, and autoimmune gastritis. Recent research is unraveling pathophysiology beyond symptom-only definitions, focusing on the duodenum with innate immune disturbance (duodenal eosinophilia) and microbial disruption as possible cause. Management of functional dyspepsia includes making a secure diagnosis, treatment with first-line proton pump inhibitors (PPI), then tricyclic antidepressants, and careful choice of prokinetics. Herbal treatments (peppermint oil) and STW-5 have in this age group limited efficacy. Further studies are needed to define the prevalence of functional dyspepsia in the elderly and of prime importance, to exclude organic disease as a cause for symptoms of dyspepsia.

P5393Deficiency of the long noncoding RNA NEAT1 disturbs T cell and monocyte-macrophage lineage differentiation and functions and results in systemic inflammation with high circulating interferon levels

Abstract Background Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs, long noncoding RNAs (lncRNAs) are implicated in inflammation control. To obtain further information on the role of lncRNAs in the context of atherosclerosis, we analyzed transcriptome maps of circulating immune cells (PBMCs) of post-MI patients in whom the lncRNA NEAT1 was suppressed. Here, we report immune disturbances in murine NEAT1 knockout models with wildtype or ApoE−/− genetic background. Methods and results RNA-sequencing (RNA-seq) of PBMCs from post-MI patients revealed profound transcriptome disturbances compared to healthy controls. Among these, NEAT1 suppression was notable since it affected the most highly expressed lncRNA as part of a molecular circuit also encompassing chemokines and interleukins. We used NEAT1−/− mice to evaluate whether NEAT1 depletion per se may cause immune dysfunction. NEAT1−/− splenocytes displayed enhanced baseline ROS production, and RNA-seq identified anomalous expression and regulation of chemokines/ receptors, innate immunity genes, TNF and caspases. FACS revealed displayed anomalous Treg and TH cell differentiation in NEAT1−/− spleens vs. wildtype (WT). Beyond grossly altered transcriptome, NEAT1−/− bone marrow derived macrophages (BMDMs) responded to LPS with increased (p&lt;0.001) ROS production, enhanced baseline phagocytic activity (p&lt;0.001), and attenuated proliferation (p=0.001). FACS revealed deregulated monocyte-macrophage differentiation in NEAT1−/− bone marrow and blood. Further, NEAT1−/− mice displayed aortic wall CD68+ cell infiltration and there was evidence of myocardial inflammation which could lead to severe and potentially life-threatening structural damage in some of these animals. This observation suggests that even stochastic activation of the highly unstable NEAT1−/− immune system may trigger uncontrolled pathogenic cascades, explaining the survival disadvantage of NEAT1−/− mice. In addition to these studies on homozygous NEAT1−/− deficiency in WT background, we obtained data on mice with partial i.e. heterozygous NEAT1−/+ deficiency on ApoE−/− background. Analysis of this new NEAT1−/+ ApoE−/− strain indicates that even partial NEAT1 deficiency leads to systemic inflammation with high IFN-gamma levels, when the animals are exposed to immune stress e.g. high LDL cholesterol. Conclusions Regarding the monocyte-enriched NEAT1 suppressed in post-MI PBMCs, the data from NEAT1−/− and NEAT1−/+ ApoE−/− mice document NEAT1 as a key immune system coordinator whose deficiency affects monocyte-macrophage and T cell differentiation and functions and renders the immune system unstable and highly vulnerable to immune stress. Since in patients NEAT1 is part of a molecular circuit persistently deregulated post-MI, too, it appears reasonable to further search for new therapeutic targets within this circuit, taking advantage of the described genetic animal models.

Seasonal alterations in the expression of inflammatory cytokines and cortisol concentrations in periparturient Sahiwal cows

ABSTRACT Heat stress during the transition period of dairy cows disturbs the homeostasis of their physiology and ultimately their health and production. Our objective was to study the seasonal variations of plasma cortisol levels and the expression of inflammatory cytokines in the peripheral blood mononuclear cells (PBMC) of 12 periparturient Sahiwal cows. Blood samples were obtained at weekly intervals from three weeks prepartum to three weeks postpartum during the winter (Temperature–humidity index, THI = 59.7) and summer (THI = 81.5) seasons. Gene expression study of pro-inflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines was done by RT-PCR and plasma cortisol by sandwich ELISA. The plasma concentration of cortisol and the relative mRNA expression of various inflammatory cytokines in PBMC were higher (p< 0.01) in the summer compared to winter season irrespective of the days of the transition period. Highest levels of cortisol and greater expression of pro-inflammatory cytokines were recorded on the day of calving in both seasons. Our study showed a higher inflammatory response, immune disturbance and greater levels of the stress hormone (cortisol) during the summer season, particularly on the day of calving.

Antioxidant Capacity and Behavioral Relevance of a Polyphenolic Extract of Chrysanthellum americanum in a Rat Model of Irritable Bowel Syndrome.

Chrysanthellum americanum L. (Vatke) is a medicinal plant from the Compositae family used in west-African traditional medicine, known for its flavonoid and saponin richness and for its strong antioxidant potential. In the present study, we assessed the effects of Chrysanthellum americanum polyphenolic extract in the psychological stress-induced rat model of irritable bowel syndrome (IBS), a chronic functional digestive tract disorder marked by immune and inflammatory-related disturbances of central nervous and peripheral intestinal systems, which is often associated with mood disorders including depression and anxiety. Consequently, memory impairment, anxiety and depression behavioral indicators, and cerebral oxidative stress biomarker dynamics were evaluated in a multifactorial heterotypic stress-exposed IBS rats after 6-day gavage with polyphenolic C. americanum extract (100 mg/kg body weight). Y-maze, elevated plus maze, and forced swimming tests were used for assessing behavioral responses. Administration of the extract exhibited significant anxiolytic and antidepressant-like effects coupled with significantly increased temporal lobe antioxidant enzyme specific activity (superoxide dismutase and glutathione peroxidase) and decreased malondialdehyde levels, a well-known lipid peroxidation marker. Furthermore, linear regression statistical analyses showed significant correlations between the oxidative stress parameters and behavioral tests. In conclusion, our results suggest that the administration of Chrysanthellum americanum polyphenolic extract could ameliorate mood and cognitive disturbances related to stress-induced in an IBS rat model. This could be also related to cerebral oxidative stress status attenuation.

Preoperative biliary drainage for resectable or borderline resectable periampullary tumor: what is the best management?

Management of preoperative biliary drainage (PBD) in patients undergoing pancreaticoduodenectomy (PD) is still debated. Obstructive jaundice is associated with a proinflammatory state, impaired immune function and disturbances in coagulation. Patients with jaundice are at high risk to develop renal dysfunction and bacteriobilia. In this context, PBD was traditionally performed before surgery to improve postoperative outcomes.

Early nutrition and gut microbiome: interrelationship between bacterial metabolism, immune system, brain structure, and neurodevelopment.

Disturbances of diet during pregnancy and early postnatal life may impact colonization of gut microbiota during early life, which could influence infant health, leading to potential long-lasting consequences later in life. This is a nonsystematic review that explores the recent scientific literature to provide a general perspective of this broad topic. Several studies have shown that gut microbiota composition is related to changes in metabolism, energy balance, and immune system disturbances through interaction between microbiota metabolites and host receptors by the gut-brain axis. Moreover, recent clinical studies suggest that an intestinal dysbiosis in gut microbiota may result in cognitive disorders and behavioral problems. Furthermore, recent research in the field of brain imaging focused on the study of the relationship between gut microbial ecology and large-scale brain networks, which will help to decipher the influence of the microbiome on brain function and potentially will serve to identify multiple mediators of the gut-brain axis. Thus, knowledge about optimal nutrition by modulating gut microbiota-brain axis activity will allow a better understanding of the molecular mechanisms involved in the crosstalk between gut microbiota and the developing brain during critical windows. In addition, this knowledge will open new avenues for developing novel microbiota-modulating based diet interventions during pregnancy and early life to prevent metabolic disorders, as well as neurodevelopmental deficits and brain functional disorders.

Potential application of helminth therapy for resolution of neuroinflammation in neuropsychiatric disorders.

Neuropsychiatric disorders (NPDs) are among the major debilitating disorders worldwide with multiple etiological factors. However, in recent years, psychoneuroimmunology uncovered the role of inflammatory condition and autoimmune disorders in the etiopathogenesis of different NPDs. Hence, resolution of inflammation is a new therapeutic target of NPDs. On the other hand, Helminth infections are among the most prevalent infectious diseases in underdeveloped countries, which usually caused chronic infections with minor clinical symptoms. Remarkably, helminths are among the master regulator of inflammatory reactions and epidemiological studies have shown an inverse association between prevalence of autoimmune disorders with these infections. As such, changes of intestinal microbiota are known to be associated with inflammatory conditions in various NPDs. Conversely, helminth colonization alters the intestinal microbiota composition that leads to suppression of intestinal inflammation. In animal models and human studies, helminths or their antigens have shown to be protected against severe autoimmune and allergic disorders, decline the intensity of inflammatory reactions and improved clinical symptoms of the patients. Therefore, "helminthic therapy" have been used for modulation of immune disturbances in different autoimmunity illnesses, such as Multiple Sclerosis (MS) and Inflammatory Bowel Disease (IBD). Here, it is proposed that "helminthic therapy" is able to ameliorate neuroinflammation of NPDs through immunomodulation of inflammatory reactions and alteration of microbiota composition. This review discusses the potential application of "helminthic therapy" for resolution of neuroinflammation inNPDs.

Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity

Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+ macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc−/−IL2rg−/− mice by adoptive transfer drives adipose fibrogenesis through activation of TGFβ1 signaling; however, transfer of Ifng−/− ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.