A Review on the Immunomodulatory Mechanism of Acupuncture in the Treatment of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with a high prevalence and canceration rate. The immune disorder is one of the recognized mechanisms. Acupuncture is widely used to treat patients with IBD. In recent years, an increasing number of studies have proven the effectiveness of acupuncture in the treatment of IBD, and some progress has been made in the mechanism. In this paper, we reviewed the studies related to acupuncture for IBD and focused on the immunomodulatory mechanism. We found that acupuncture could regulate the innate and adaptive immunity of IBD patients in many ways. Acupuncture exerts innate immunomodulatory effects by regulating intestinal epithelial barrier, toll-like receptors, NLRP3 inflammasomes, oxidative stress, and endoplasmic reticulum stress and exerts adaptive immunomodulation by regulating the balance of Th17/Treg and Th1/Th2 cells. In addition, acupuncture can also regulate intestinal flora.

Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

Effects of Lactobacillus on Interleukin-4 (IL-4), Tumour Necrosis Factor-Alpha (TNF-Alpha) and Immune Function in Allergic Rhinitis Rats

Allergic rhinitis (AR) is a type of nasal mucosal inflammation. Lactobacillus plays a critical role in maintaining micro-ecological balance. This study aims to detect its effects on IL-4, TNF-α, Th1 and Th2 in AR sprapue-dawley (SD) rat after lactobacillus intervention. Ovalbumin (OVA) allergic AR SD rat model was established and assigned into model group, experimental group and blank group followed by analysis of Nasal mucosa under the microscope, IL-4 and TNF-α level by ELISA and immunohistochemistry assay, and Th1 and Th2 cells in spleen by flow cytometry. AR symptom in experimental group was significantly severe compared to blank group, but relative better compared to model group (p < 0.05). Nasal mucosal hyperemia and inflammation was significantly ameliorated in experimental group with significantly increased Th1 cells and Th1/Th2 ratio and decreased Th2 cells compared to model group (p < 0.05). In conclusion, Lactobacillus intervention reduced IL-4 and TNF-α expression in serum and tissue and ameliorated the inflammation in AR rat.

Decreased Absolute Number of Circulating Regulatory T Cells in Patients With Takayasu’s Arteritis

BackgroundTakayasu’s arteritis (TA) is a type of primary large vessel vasculitis. Th1, Th17, and Tfh cells have been reported to be associated with TA relapse. However, the relationship between regulatory T cells (Tregs) and TA remains unclear.ObjectiveTo analyze the levels of circulating lymphocytes, especially Treg cells (CD4+CD25+FOXP3+ T cells) and serum cytokines in TA patients and explore their relationship with their changes and TA disease activity.MethodsA total of 57 TA patients and 43 sex- and age-matched healthy controls (HCs) were enrolled. According to NIH standards, 36 patients had active disease status. Flow cytometry combined with counting was used to detect the absolute numbers and ratios of Th1, Th2, Th17, and Treg cells in the peripheral blood of all the subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines.ResultsCompared to HCs, the absolute number and proportion of peripheral Treg cells in TA patients was significantly decreased, while Th17 cells were significantly increased. Furthermore, compared to the inactive group, the TA active group had significantly increased levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, but lower IL-10 levels. The absolute number of Th2 cells was negatively associated with platelet (PLT) and NIS scores in TA patients. The proportion of Th2 cells was negatively associated with the erythrocyte sedimentation rate in TA patients. After treatment, Treg cells were markedly increased.ConclusionThere was a Th17-Treg cell imbalance with a significant reduction in peripheral Treg cells and an increase in Th17 cells in TA patients compared to the HCs. The levels of IL-6, IL-10, IL-17, and TNF-α appeared to be related to disease activity.

Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

The COVID-19 pandemic has led to several pioneering scientific discoveries resulting in no effective solutions with the exception of vaccination. Moderate exercise is a significant non-pharmacological strategy, to reduce the infection-related burden of COVID-19, especially in patients who are obese, elderly, and with additional comorbidities. The imbalance of T helper type 1 (Th1) or T helper type 2 (Th2) cells has been well documented among populations who have suffered as a result of the COVID-19 pandemic, and who are at maximum risk of infection and mortality. Moderate and low intensity exercise can benefit persons at risk from the disease and survivors by favorable modulation in Th1/Th2 ratios. Moreover, in COVID-19 patients, mild to moderate intensity aerobic exercise also increases immune system function but high intensity aerobic exercise may have adverse effects on immune responses. In addition, sustained hypoxia in COVID-19 patients has been reported to cause organ failure and cell death. Hypoxic conditions have also been highlighted to be triggered in COVID-19-susceptible individuals and COVID-19 survivors. This suggests that hypoxia inducible factor (HIF 1α) might be an important focus for researchers investigating effective strategies to minimize the effects of the pandemic. Intermittent hypoxic preconditioning (IHP) is a method of exposing subjects to short bouts of moderate hypoxia interspersed with brief periods of normal oxygen concentrations (recovery). This methodology inhibits the production of pro-inflammatory factors, activates HIF-1α to activate target genes, and subsequently leads to a higher production of red blood cells and hemoglobin. This increases angiogenesis and increases oxygen transport capacity. These factors can help alleviate virus induced cardiopulmonary hemodynamic disorders and endothelial dysfunction. Therefore, during the COVID-19 pandemic we propose that populations should engage in low to moderate exercise individually designed, prescribed and specific, that utilizes IHP including pranayama (yoga), swimming and high-altitude hiking exercise. This would be beneficial in affecting HIF-1α to combat the disease and its severity. Therefore, the promotion of certain exercises should be considered by all sections of the population. However, exercise recommendations and prescription for COVID-19 patients should be structured to match individual levels of capability and adaptability.

On the Relationship Between Serum Level of Interleukin-33 with Allergic Rhinitis and Its Severity in Children

Background: T helper type 2 (Th2) cells are critical cellular elements in allergic rhinitis. Interleukin-33 (IL-33) produces Th2-related cytokines and binds to the ST2 receptors. This is expressed strongly in mastocytes and discerningly in Th2 cells. Through Th2 cells, IL-33 may also have partly involved in immune responses. Objectives: This study aimed to measure the IL-33 serum levels in children suffering from allergic rhinitis and investigate its relationship with the disease. Methods: This case-control study was conducted on a population with the age range of 7-18 years, who referred to the Pediatric Clinic of the Shahid Beheshti Hospital in Kashan, Iran, in 2017. The study sample encompassed 57 patients with allergic rhinitis (case group) and 57 subjects with no allergic rhinitis (control group). The ELISA assay was used to measure the serum level of IL-33 in the case and control groups. Allergic rhinitis was diagnosed by a pediatric immunologist considering the patient’s history and the guidelines set out by the Allergic Rhinitis and its Impact on Asthma (ARIA). All study data were analyzed with SPSS software version 22. Results: There were significant differences between the two groups in terms of age (P = 0.001), gender (P = 0.0144), family history of atopy (P < 0.001), symptoms duration (P < 0.001), and comorbidities (e.g., atopic dermatitis and asthma) (P < 0.001). Furthermore, compared to the control group, the case group exhibited significantly higher IL-33 serum levels (P < 0.001). Conclusions: The high serum levels of IL-33 exhibited in patients with allergic rhinitis indicate its involvement in the pathogenesis of the concerned disease.

What is the Role of Vitamin D in the Severity and Control of Asthma in Children and Adolescents: a Protocol for a Systematic Review

Background: Vitamin D plays an important role in the immune system and consequently in the inflammatory process of asthma. It acts directly on the regulation of Th1 and Th2 cells and regulatory T lymphocytes. Evidence shows that vitamin D can act on dendritic cells, raising inflammatory mediators and increasing the imbalance between Th1, Th2, and Th17. Understanding the link between vitamin D and inflammatory processes in the control and severity of asthma is important for the existence of specific therapies. Objective: We aim to synthesize the scientific evidence about the role of Vitamin D in the control and severity of asthma in pediatric patients by a systematic review. Methods: A systematic and comprehensive search will be performed using MEDLINE PubMed, BIREME, EBSCOhost, Scopus, Web of Science, EMBASE, Cochrane Library, and ProQuest. From the data obtained, all the articles found will be transferred to the Rayyan platform. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist (PRISMA-2020). Additionally, if sufficient data are available, a meta-analysis will be conducted.Discussion: The ability of vitamin D to act in the immune system with a direct action on the inflammatory asthma cascade, allows for a better understanding of the disease. This will lead to better asthma management, and, consequently, to help in controlling the disease. The conduction of a systematic review will bring better knowledge about vitamin D and its role in the pathophysiology of asthma Systematic review registration:This protocol has been registered in the PROSPERO and the registration number is CRD42021221638.

Genotype and Th2 cells control monocyte to tissue resident macrophage differentiation during nematode infection of the pleural cavity

The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed in the C57BL/6 strain. Here, we provide a comprehensive analysis of immune cells in the pleural cavity using both C57BL/6 and BALB/c mice. Unlike C57BL/6 mice, naive tissue-resident Large Cavity Macrophages (LCM) of BALB/c mice failed to fully implement the tissue residency program. Following infection with a pleural-dwelling nematode these pre-existing differences were accentuated with LCM expansion occurring in C57BL/6 but not BALB/c mice. While infection drove monocyte recruitment in both strains, only in C57BL/6 mice were monocytes able to efficiently integrate into the resident pool. Monocyte to macrophage conversion required both T cells and IL-4Rα signalling. Host genetics are therefore a key influence on tissue resident macrophage biology, and during nematode infection Th2 cells control the differentiation pathway of tissue resident macrophages.

Distinct functions of genome-wide chromatin remodeling in the differentiation of T helper Type 1 and 2 cells

T helper type 1 and 2 (Th1 and Th2) cells play critical roles in infectious, autoimmune and allergic diseases. Here we mapped genome-wide distribution of DNase I hypersensitive (DHS) sites in Th1, Th2 and their precursors naïve CD4 T cells. DHS sites were found unevenly distributed in the genomes with highest densities within 2kb of the transcription start sites (TSS). At the whole genome level, the DHS values, representing chromatin openness, but not the numbers of DHS sites showed strong positive correlation with gene expression. Th1 and Th2 differentiations were accompanied by changes of genome-wide distribution of DHS sites. The differentiated cells assumed more open chromatin structures than their precursors. During Th1 differentiation changes of DHS values could be statistically positively or negatively associated with changes of gene expression depending on the locations of the DHS sites, whereas only positive association was found during Th2 differentiation.

Preserved T-cell Response in anti-CD20 Treated Multiple Sclerosis Patients Following SARS-CoV-2 Vaccination

The SARS-CoV-2 pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). We here investigated humoral and cellular immune responses, including neutralization against SARS-CoV-2 WT and delta variant and T cell responses of aCD20-treated MS patients following SARS-CoV-2 vaccination compared to healthy controls. aCD20-treated MS patients had lower anti-SARS-CoV-2-Spike titers, which correlated with B-cell repopulation. Sera of aCD20 treated patients had reduced capacity to neutralize WT and delta pseudoviruses in vitro. On the contrary, aCD20 treated patients elicited higher frequencies of CD3+ T cells, Th1 cells, Th2 cells, Tc1 cells and CD8+IFN-γ+IL-2+ cells. In summary, aCD20 treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with a shift of cellular immune response to a stronger Th1, Th2 and Tc1 phenotype, suggesting strong cellular protection against SARS-CoV-2.