The regulation of tolerogenic dendritic cells by a Chinese herb formula improves abortion prone in mice.

BACKGROUND: Abortion prone (AP) is a common clinical event. The underlying mechanism remains unclear. Traditional Chinese formulas are known to be efficient in the management of abortion. The purpose of this study is to observe the effects of Anzitiaochongtang (AZT), a traditional formulation of Chinese medicine, on improving AP in mice by regulating immune tolerance. METHODS: An established abortion model (CBA/J×DBA/2) was employed. AZT was prepared and administered to mice in a manner consistent with clinical practice. Tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cell) in mice were analyzed by immunological approaches to be used as representative immune tolerant parameters. RESULTS: An AP model was established with CBA/J × DBA/2 mice. The expression of IL-10 in tDC and Tr1 cell frequency in the mouse decidua tissues were lower in the AP group than that in the normal pregnancy (NP) group. Administration of AZT up regulated the expression of IL-10 in tDCs and Tr1 cell generation in the decidua tissues, and improved the pregnancy and tissue structure in AP mice. The main mechanism by which AZT improves pregnancy in AP mice is that AZT enhanced the expression of galectin-9 in the epithelial cells of decidua tissues. Galectin 9 activates TIM3 on DCs to promote the IL-10 expression. The DCs induced more Tr1 cells in the decidua tissues. CONCLUSIONS: Dysfunctional tDCs were detected in the AP decidua tissues. Administration of AZT improved pregnancy in AP mice by regulating tDC function and generation of Tr1 cells in the maternal-fetal interface.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells.

The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.

Identification of antigen-specific neutrophils in the tonsils with recurrent acute inflammation.

The pathogenesis of recurrent acute tonsillitis (Rtn) is to be further investigated. Polymorphonuclear neutrophils (PMN) often associate with the pathogenesis of acute and chronic inflammation. This study aims to identify the antigen-specific PMNs (sPMNs) isolated from the tonsillar tissues with recurrent acute inflammation. In this study, CD66b+ PMNs were isolated from surgically removed tonsils (40 tonsils were from 20 Rtn patients; 24 tonsils were from 12 tonsil tumour patients) by flow cytometry cell sorting. sPMNs were identified through immunological approaches. We found that compared with the control tonsil samples (from marginal non-tumour tissues of tonsil cancer), Rtn samples showed higher PMN frequency, higher levels of myeloperoxidase (MPO) and neutrophil elastase (NE), in which positive correlation was detected between the inflammatory scores in the Rtn tissues and PMN counts (r = .7352; p = .0002), or MPO (r = .6565, p = .0017), or NE (r = .6687, p = .0013). Upon exposure to tonsillar tissue protein extracts in the culture, a portion of Rtn PMNs was activated and released inflammatory mediators. A complex of tonsillar tissue-specific IgG and FcγRI was observed on the surface of Rtn PMNs; these PMNs could specifically recognize the Rtn tissue extracts and were designated the tonsillar antigen-specific PMNs (sPMNs). A signal transduction pathway of mitogen-activated protein kinase (MAPK)-nuclear factor of T cell activation (NFAT) was activated in sPMNs after exposure to Rtn tissue extracts. In summary, a fraction of sPMN in the Rtn tonsillar tissues was identified and characterized. The sPMNs can be activated upon exposure to tonsil-specific antigens. These sPMNs may contribute to the Rtn pathogenesis.

Herbal Formula-3 ameliorates OVA-induced food allergy in mice may via modulating the gut microbiota.

Formula-3 is a Chinese herbal medicine formula that was shown to inhibit food allergy in rats by stabilizing mast cells. But whether Formula-3 ameliorates food allergy through modulating the composition of intestinal microbiota remains to be explored. Here, we aimed to determine whether gut microbiota mediate the anti-food allergic effects of Formula-3. Mouse model of food allergy (FA) was induced by intragastrically administered with ovalbumin and cholera toxin for two weeks, then these mice were orally administrated daily with 1 ml PBS (0.1 mmol/L) or 1 ml Formula-3 (100 mg/m1) for four weeks. The number and abundance of gut mircrobiota were measured with 16S rRNA gene sequencing. We found administration of Formula-3 significantly alleviated FA by decreasing the serum levels of specific IgE, and Th2 cytokine IL-4, IL-5, and IL-13. The dominant characteristics of gut microbiota in mice with FA was the increase in Firmicutes and decrease in Bacteroidetes, and the emergence of Deferribacteres. Formula-3 treatment partially reversed the gut bacterial dysbiosis via increasing Bacteroidetes and decreasing Firmicutes. Moreover, Formula-3 decreased the bacteria from Prevotella, Moryella and Clostridium, and increased Rikenella. Functional analysis indicated modules involved in phosphotransferase system and lipopolysaccharide biosynthesis were enriched in FA mice, while Formula-3 treatment enriched pathways of multiple transport system. Our study reveals that Formula-3 may ameliorate food allergy through modulating the bacterial dysbiosis.

Retracted Article: Anti-inflammatory potency of Locusta migratoria manilensis cyclopeptides in mast cells and macrophages.

Locusts are esteemed as a traditional Chinese medicine, as well as tonic foods in Asian countries. While searching for natural anti-inflammatory agents in natural products, we isolated four novel locust cyclopeptides (LCPs) and the results show that [cyclo-(Trp-Leu-His-Thr)]∼LCP-3 has potent anti-inflammatory potency in RAW264.7 and HMC-1 cells under LPS (lipopolysaccharide) stimuli. Furthermore, mechanistic studies show that LCP-3 attenuates pro-inflammatory cytokine (TNF-α, IL-6, IL-1ß, NO and PGE2) expression. Moreover, LCP-3 attenuates inflammatory damage associated with the direct inhibition of iNOS and COX-2 expression. LCP-3 also regulates the MAPK, PI3K/AKT and NF-κB pathways to attenuate LPS-induced damage. Of note, our study first reports the anti-inflammatory potency of LCPs and elucidates their underlying molecular mechanisms.

Identification and characterization of a pan-allergen profilin, a major allergen from Caryota mitis pollen.

BACKGROUND: Caryota mitis is a common plant in tropical and subtropical areas. It produces larger amount of pollen, which has great potential for allergenicity in the pollination season. OBJECTIVE: This study aims to identify the components of Caryota mitis pollen contributing to human allergic diseases. METHODS: The sera from 20 patients with a positive skin prick test to Caryota mitis pollen crude extract (CmPCE) were collected; the allergic components were determined by the forming of immune complexes in the sera and CmPCE. The results were confirmed by the immune competitive inhibitory assay. RESULTS: Sixteen out of 20 collected serum samples reacted to a 14 kDa protein fractioned from CmPCE; this 14 kDa antigen also had positive reactions to CmPCE in an ELISA assay. 12 samples from 20 collected serums positively reacted to recombinant CmProfilin (rCmProfilin), as shown by Western blotting, and also showed positive reactivity in ELISA. Preincubation of sera with rCmProfilin eliminated the reactivity of the patients' sera to this 14 kDa band. CONCLUSION: A 14 kDa protein from the CmPCE was identified as the major allergic component of CmPCE.

An investigation of airborne allergenic pollen at different heights.

BACKGROUND AND AIMS: Airborne pollen is an important source of allergens in a number of allergic diseases. Data on the concentrations of pollen at different heights in the air are scarce. The aim of the present study was to investigate different types and numbers of airborne pollen and their seasonal variation at different heights in the urban area of Shenzhen (China) and their associations with meteorological factors. METHODS: The concentration of airborne pollen at different heights was monitored with Burkard traps from July 1, 2006, to June 30, 2007, in Shenzhen; the results were analyzed with SAS 9.13 software. RESULTS: In total, 1,095 films (at 3 heights, 365 films at each height) were exposed throughout the year, and 48 families and 85 genera of pollen taxa were identified. The total pollen count was 55,830 grains (25,204 grains at 1.5 m; 16,218 grains at 35 m, and 14,408 grains at 70 m); pollen grains were present in the atmosphere throughout the year, with two peaks of airborne pollen: one peak in February to April and the other in September to November. CONCLUSIONS: On the basis of our local investigations, the pollen concentrations and the pollen types in the air decrease gradually with increasing height. The distribution and concentrations of airborne pollen at different heights in the atmosphere were influenced by composite factors such as the season and meteorological factors.

Modulation of immune tolerance with a Chinese traditional prescription inhibits allergic rhinitis in mice.

BACKGROUND: Allergic diseases substantially affect human health and social economy. The pathogenesis is to be further understood. The effect of current therapeutic remedies on allergic diseases is not satisfactory. AIMS: This study aimed to inhibit allergic rhinitis in a mouse model with a Chinese traditional medical prescription, Bu-Zhong-Yi-Qi-Tang. MATERIAL AND METHODS: A mouse AR model was developed with ovalbumin (OVA) plus adjuvant alum. The AR clinical symptoms and immune pathology in the nasal mucosa were assessed with the AR mouse model. Some mice were treated with Bu-Zhong-Yi-Qi-Tang via gavage-fed. The immune tolerance status in the nasal mucosa was evaluated by counting the numbers of tolerogenic dendritic cells (DC) and regulatory T cells (Treg). RESULTS: After exposure to the specific antigen, OVA, the sensitized mice had AR-like symptoms including nasal itch and sneeze. The frequency of mast cells, levels of IgE/IL-4 in nasal mucosa was markedly higher in sensitized mice than naïve controls; while the levels of integration alphavbeta6 (avb6), the number of tolerogenic DCs and Tregs in nasal mucosa were significantly lower than naïve control mice. The AR-like symptoms and immune pathology and immune tolerance status in the AR nasal mucosa were substantially improved by administration with Bu-Zhong-Yi-Qi-Tang. CONCLUSIONS: The immune tolerance status is impaired in the AR nasal mucosa that can be improved by administering with Bu-Zhong-Yi-Qi-Tang.