Modulating endoplasmic reticulum stress attenuates mast cell degranulation.

OBJECTIVES: Degranulation of mast cells leads to direct allergic symptoms. The underlying mechanism needs to be explored further. Endoplasmic reticulum (ER) stress is involved in the pathogenesis of allergic conditions. The objective of this study is to gain a better understanding of the mechanism of mast cell degranulation. METHODS: Bone marrow derived mast cells and mast cells isolated from the airway tissues were prepared. The role of ER stress in mediating the release of mast cells was tested. RNA sequencing (RNAseq) was used to investigate the genetic activities of mast cells. RESULTS: Our observation showed that sensitization increased ER stress in mast cells. X-box-1 binding protein (XBP1) activity was linked to mast cell degranulation. Modulation of ER stress or XBP1 expression regulates the release of the mast cell mediator. XBP1 promoted the mediator release of mast cells by activating spleen tyrosine kinase (Syk). Activation of eukaryotic initiation factor 2a (eIF2a) inhibited XBP1 in mast cells. Semaphorin 3A was effective in preventing experimental allergic rhinitis (AR) due to its ability to suppress the release of mast cell mediators. CONCLUSIONS: ER stress is associated with the mast cell degranulation. By inhibiting XBP1, the crucial molecule of ER stress, mast cell degranulation can be suppressed and experimental AR can be mitigated.

[A study of airborne pollen monitoring and its connection with allergic rhinitis visits in Taiyuan over the summer and autumn seasons].

Objective:To explore the distribution of airborne pollen in summer and autumn in Taiyuan, analyze the correlation between pollen characteristics, meteorological factors and allergic sensitization, and provide for the prevention and treatment of allergic diseases in this. Methods:The gravity sedimentation method was used to investigate the types, quantities and dispersion patterns of airborne pollen in Taiyuan City from July 21, 2022 to October 20, 2022. he meteorological and patient information was collected during the same period SPSS 26.0 software. Results:①A total of 17 118 pollen grains were collected, and identified as 14 families, 10 genera, and 4 species. The peak period for pollen dispersal in summer and autumn in Taiyuan City from late August to early September. airborne pollen Artemisia（66.62%）, Cannabis/Humulus（17.79%）, Sophora japonica（8.18%）, Chenopodiaceae/Amaranthaceae（2.83%）, Gramineae（2.11%）. ②The concentration of airborne pollen in Taiyuan City positively correlated with the average temperature（5-20℃） and maximum temperature（11-30℃） within a certain range（r=0.547, 0.315, P<0.05）. ③The content of airborne pollen in Taiyuan City positively correlated with the number of visits and allergen positive rate of patients with allergic rhinitis（AR） in our hospital（r=0.702, 0.747, P<0.05）. Conclusion:The peak period for airborne pollen dispersal during the summer and autumn seasons in Taiyuan City from late August to early September. The dominant pollen is Artemisia, Cannabis/Humulus, Sophora japonica, Chenopodiaceae/Amaranthaceae, Gramineae, and the absolute advantage pollen is Artemisia. Meteorological factors pollen content. Within a certain range, temperature the diffusion and transportation of pollen. The number of pollen grains the number of visits, which can serve as an environmental warning indicator for AR patients to take preventive, thereby reducing the risk of allergies.

Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy.

Sustaining higher frequency of mast cells in the allergic lesion site has been recognized. Factors causing high numbers of mast cells in the local tissues are not fully understood yet. RAS signaling plays a role in sustaining certain cell activities. This study is aimed at elucidating the role of RAS activation in the apoptosis resistance induction in mast cells and at employing semaphorin 3A to regulate RAS activities in sensitized mast cells and alleviating the allergic response in the intestine. A food allergy (FA) mouse model was developed. Mast cells were isolated from FA mouse intestinal tissues by flow cytometry. Mast cell apoptosis was assessed by staining with annexin V and propidium iodide. We found that aberrantly higher p21-activated kinase-1 (Pak1) expression in FA mast cells was associated with mast cell aggregation in the intestine. Sensitization increased Pak1 expression and apoptosis resistance in intestinal mast cells. RAS and Pak1 mutually potentiated each other in sensitized mast cells. Semaphorin 3A (sema3A) suppressed the Pak1 expression and RAS activation in mast cells. sema3A restored the apoptosis sensitivity in sensitized mast cells. Administration of sema3A potentiated allergen-specific immunotherapy in experimental FA. In conclusion, mast cells of FA mice showed higher Pak1 expression and high RAS activation status that contributed to apoptosis resistance in mast cells. Administration of sema3A restored the sensitivity to apoptosis inducers and promoted the therapeutic effects of specific immunotherapy on experimental FA.

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.