The Immune Regulatory Functions in B Cells Are Restored by CpG to Reduce Experimental Food Allergy.

Dysfunctional immune regulation contributes to the pathogenesis of food allergy (FA). The mechanism behind regulatory B-cell dysfunction is unclear. CpG has immune regulatory functions. The purpose of this study is to use CpG to recover the immune suppressive functions of B cells in mice with FA. An FA mouse model was created using ovalbumin as the specific antigen. Flow cytometry was used to isolate B cells from the intestinal tissues. The immune regulatory functions of B cells were assessed using immunological approaches. The results showed that the FA response was linked to low IL-10 levels in gut lavage fluids of FA mice. FA mouse intestinal B cells produced lower amounts of IL-10 as compared with B cells isolated from naïve control mice. Impaired immune suppressive functions were observed in B cells isolated from the FA mouse intestine. The inducibility of the Il10 expression in naïve B cells of the intestine of FA mice was defective. The induction of Il10 expression in FA B cells could be restored by CpG through regulating the methylation status of the Cmip promoter. CpG promoted the therapeutic efficacy of allergen specific immunotherapy by restoring the induction of IL-10+ B cells in the intestine. The expression of Il10 in B cells of the FA mouse intestine was impaired. Administration of CpG could restore the expression of Il10 in B cells in the intestine and promote immunotherapy for FA.

The relationship between follicle-stimulating hormone and metabolic dysfunction-associated fatty liver disease in men.

OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

Identification of mite-specific eosinophils in the colon of patients with ulcerative colitis.

The pathogenesis of ulcerative colitis (UC) is unclear. House dust mite (HDM) is associated with immune inflammation in the body. This study is designed to identify the association between HDM and UC clinical symptoms. UC patients (n = 86) and non-UC control (NC) subjects (n = 64) were recruited. Colon lavage fluids (CLF) were collected from HDM skin prick test positive patients during colonoscopy, and analyzed by immunological approaches. HDM was detected in fecal samples, which was positively correlated with UC clinical symptoms. HDM-specific eosinophils and Th2 cells were detected in CLF, which could be specifically activated by exposing to HDM in the culture. Direct exposure to HDM induced eosinophil activation in the colon of UC patients. UC patients displayed elevated levels of Th2 cytokines in the serum. UC clinical symptom scores were positively correlated with serum levels of Th2 cytokines. HDM was detected in UC patients' stools, which was positively correlated with UC clinical symptoms. Direct exposure to HDM could trigger eosinophilic activation of the colon.

Propionic acid regulates immune tolerant properties in B Cells.

Interleukin 10 (IL-10)-producing B cells (B10 cells) are a canonical cell fraction for regulating other activities of immune cells. Posttranscriptional modification of IL-10 in B10 cells is not yet fully understood. Short-chain fatty acids play an important role to regulate the functions of immune cells. This study aims to clarify the role of propionic acid (PA), a short-chain fatty acid, in regulating the expression of IL-10 in B10 cells. Blood samples were collected from patients with food allergy (FA) and healthy subjects. Serum and cellular components were prepared with the samples, and analysed by enzyme-linked immunosorbent assay and flow cytometry, respectively. The results showed that serum PA levels were lower in FA patients. PA concentrations were negatively correlated with serum cytokine Th2 concentrations, specific IgE concentrations in serum and skin prick test results. The peripheral frequency of B10 cells and the production of IL-10 in B cells were also associated with serum PA concentrations. Activation of B cells by CpG induced the production of IL-10 and tristetretrprolin (TTP), in which TTP caused the spontaneous decay of IL-10 mRNA. PA was necessary to stabilize the IL-10 mRNA in B cells by inducing the production of granzyme B, which resulted in the degradation of the IL-10 mRNA. Administration of PA attenuated FA response in mice by maintaining homeostasis of B10 cells. In conclusion, PA is needed to stabilize the expression of IL-10 in B10 cells. PA administration can mitigate experimental FA by maintaining B10 cell functions.

CD38+ B cells affect immunotherapy for allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases, but the therapeutic effects of AIT need to be improved. CD38+ B cells are an immune cell fraction involved in the pathogenesis of allergic diseases as well as in immune regulation. OBJECTIVE: We sought to elucidate the role of antigen-specific CD38+ B cells in AIT. METHODS: An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38+ B cells in AIT. RESULTS: A fraction of antigen-specific CD38+ B cell was detected in AR patients. CD38+ B-cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38+ B-cell frequency and regulatory T-cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38+ B cells to produce IL-6, that converted Treg cells to TH17 cells. Coadministration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT. CONCLUSIONS: Antigen-specific CD38+ B cells compromise AIT effects by producing IL-6 to convert regulatory T cells to TH17 cells. Inhibition of CD38+ B cells promotes the effects of AIT.

Acoustic Radiation Force Impulse Imaging With Virtual Touch Tissue Quantification Enables Characterization of Mild Hypoxic-Ischemic Brain Damage in Neonatal Rats.

OBJECTIVES: The aim of this study was to investigate whether the measurement of brain tissue stiffness using acoustic radiation force impulse (ARFI) elastography with virtual touch tissue quantification can improve the early detection of neonatal hypoxic-ischemic brain damage in rats. METHODS: Seven-day-old Sprague-Dawley rats were randomly assigned to 3 groups: the mild asphyxia (n = 30), moderate asphyxia (n = 30), and sham control (n = 10) groups. Rats in the mild and moderate asphyxia groups were exposed to 8% oxygen (hypoxia) for 30 and 60 minutes, respectively, at 1 hour after ligation of the right common carotid artery. An ultrasound diagnostic instrument was used to obtain 2-dimensional ultrasound images, and ARFI with virtual touch tissue quantification was used to measure shear wave velocity preoperatively and at 12, 24, 48, and 72 hours postoperatively. Hematoxylin-eosin staining was used to evaluate brain damage. RESULTS: Two-dimensional ultrasound imaging detected swelling and increased echogenicity at 48 to 72 hours in the mild asphyxia group and at 24 to 72 hours in the moderate asphyxia group. The shear wave velocity substantially increased from 0.65 ± 0.04 m/s preoperatively to 0.78 ± 0.07 m/s at 72 hours in the moderate asphyxia group and from 0.64 ± 0.04 m/s preoperatively to 0.70 ± 0.03 m/s at 72 hours in the mild asphyxia group. The changes in the shear wave velocity coincided with the histopathologic changes in the brain, which included neuronal demyelination, hyperplasia, and necrosis; edema around vascular structures; and hemorrhage in the ependymal and periventricular areas. CONCLUSION: Shear wave velocity data obtained with the virtual touch tissue quantification technique may be used for early diagnosis of neonatal hypoxic-ischemic brain damage.

[Effect of yigu capsule contained serum on mRNA and protein expression of estrogen receptor in osteoblast rats].

OBJECTIVE: To explore the effect of Yigu capsule contained serum on mRNA and protein expression of osteoblast estrogen receptor (ER), for investigating the mechanism of its preventing and treating osteoporosis by means of regulating estrogen. METHODS: Osteoblasts separated from newborn SD rats were cultured, and divided into 3 groups after being passaged, i.e. the drug-serum treated group, the blank serum group and the DMEM medium control group. The relative amount of ERalpha and ERbeta expression were determined with RT-PCR, the affinity (expressed by equilibrium dissociation constant, KD) and number of ER (RT) were analysed by radioligand assay. RESULTS: The relative amount of ERbeta mRNA expression were increased in the drug-serum group, with significant difference as compared with that in the other two groups (P < 0.05), but no significant difference among the three groups in ERa mRNA expression (P > 0.05). KD in the drug-serum group showed insignificant difference as compared with that in the other two groups (P > 0.05), but RT increased in the drug-serum group and the difference in the three groups was significant (P < 0.01). CONCLUSION: Drug-contained serum of Yigu capsule can up-regulate the expression of osteoblast ERbeta mRNA and increase the amount of ERs. Regulating estrogen is possibly one of the mechanisms of Yigu capsule in preventing and treating osteoporosis.