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Background: Propolis is a resinous mixture produced by honey bees that contains cinnamic acid derivatives and flavonoids. Although propolis has been reported to inhibit mast cell functions and mast cell-dependent allergic responses, the effect of propolis on basophil biology remains unknown. This study aimed to investigate the inhibitory effect of propolis on FcεRI-mediated basophil activation., Methods: To determine the inhibitory effect of propolis on basophil activation in vitro, cytokine production and FcεRI signal transduction were analyzed by ELISA and western blotting, respectively. To investigate the inhibitory effect of propolis in vivo, IgE-CAI and a food allergy mouse model were employed., Results: Propolis treatment resulted in the suppression of IgE/antigen-induced production of IL-4, IL-6 and IL-13 in basophils. Phosphorylation of FcεRI signaling molecules Lyn, Akt and ERK was inhibited in basophils treated with propolis. While propolis did not affect the basophil population in the treated mice, propolis did inhibit IgE-CAI. Finally, ovalbumin-induced intestinal anaphylaxis, which involves basophils and basophil-derived IL-4, was attenuated in mice prophylactically treated with propolis., Conclusions: Taken together, these results demonstrate the ability of propolis to suppress IgE-dependent basophil activation and basophil-dependent allergic inflammation. Therefore, prophylactic treatment with propolis may be useful for protection against food allergic reactions in sensitive individuals., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Basophils are an important cell type in the regulation of Th2 immune responses. Recently, we revealed that signal-transducing adaptor protein-2 (STAP-2) negatively regulates mast cell activation via FcεRI. However, the role of STAP-2 in basophil maturation and activation remained unclear. In this study, we demonstrated the normal development of basophils in STAP-2-deficient (STAP-2-/-) mice. We also demonstrated in vitro normal basophil differentiation and FcεRI expression in STAP-2-/- mice, suggesting that STAP-2 is dispensable for basophil maturation. Using bone marrow-derived cultured basophils (BMBs), we showed that degranulation and cytokine production of STAP-2-/- BMBs were lower than those of wild-type (WT) BMBs upon stimulation with IgE/Ag. In accordance with the reduction of degranulation and cytokine production, phosphorylation of several signal molecules such as Lyn, PLC-γ2 and Erk was reduced in STAP-2-/- BMBs after stimulation via FcεRI. Finally, it was observed that IgE-dependent chronic allergic inflammation of STAP-2-/- mice was significantly inhibited compared with WT mice. Taken together, we conclude that STAP-2 is an adaptor molecule that positively regulates FcεRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions., (© The Japanese Society for Immunology. 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chronic urticaria (CU) appears to be of autoimmune origin in about half of all patients, since several autoreactive immunoglobulin Gs (IgGs), such as anti-FcεRIα and anti-IgE, are detected in the sera of such patients. However, whether autoreactive IgE is associated with CU remains unclear. In this study, we attempted to identify autoreactive IgE antibodies in sera from patients with CU., Methods: Sera were collected from 67 normal subjects, 85 patients with CU and 28 patients with atopic dermatitis (AD). An autologous serum skin test (ASST) was performed on 27 of the CU patients. Autoreactive IgE and IgG levels against self-antigens were measured using enzyme-linked immunosorbent assays. The basophils were activated with dsDNA, and the CD63 expression level was examined using a fluorescence-activated cell sorter., Results: The anti-dsDNA IgE levels were significantly higher in patients with CU and AD than in normal subjects, but no differences in the anti-dsDNA IgG levels were seen. The levels of thioredoxin-, peroxiredoxin- and thyroglobulin-reactive IgE and IgG were not significantly higher in the CU patients than in the other 2 groups. There was no significant difference in the levels of anti-dsDNA IgE between ASST-positive and ASST-negative patients. The basophils from 2 out of 9 CU patients exhibited degranulation in response to dsDNA., Conclusions: Our data suggest that anti-dsDNA IgE is involved in the pathogenesis of some cases of CU., (Copyright © 2013 S. Karger AG, Basel.)

Background: Chronic urticaria (CU) appears to be of autoimmune origin in about half of all patients, since several autoreactive immunoglobulin Gs (IgGs), such as anti-FcεRIα and anti-IgE, are detected in the sera of such patients. However, whether autoreactive IgE is associated with CU remains unclear. In this study, we attempted to identify autoreactive IgE antibodies in sera from patients with CU. Methods: Sera were collected from 67 normal subjects, 85 patients with CU and 28 patients with atopic dermatitis (AD). An autologous serum skin test (ASST) was performed on 27 of the CU patients. Autoreactive IgE and IgG levels against self-antigens were measured using enzyme-linked immunosorbent assays. The basophils were activated with dsDNA, and the CD63 expression level was examined using a fluorescence-activated cell sorter. Results: The anti-dsDNA IgE levels were significantly higher in patients with CU and AD than in normal subjects, but no differences in the anti-dsDNA IgG levels were seen. The levels of thioredoxin-, peroxiredoxin- and thyroglobulin-reactive IgE and IgG were not significantly higher in the CU patients than in the other 2 groups. There was no significant difference in the levels of anti-dsDNA IgE between ASST-positive and ASST-negative patients. The basophils from 2 out of 9 CU patients exhibited degranulation in response to dsDNA. Conclusions: Our data suggest that anti-dsDNA IgE is involved in the pathogenesis of some cases of CU. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

IgE-mediated activation of mast cells and basophils underlies allergic diseases such as asthma. Histamine-releasing factor (HRF; also known as translationally controlled tumor protein [TCTP] and fortilin) has been implicated in late-phase allergic reactions (LPRs) and chronic allergic inflammation, but its functions during asthma are not well understood. Here, we identified a subset of IgE and IgG antibodies as HRF-interacting molecules in vitro. HRF was able to dimerize and bind to Igs via interactions of its N-terminal and internal regions with the Fab region of Igs. Therefore, HRF together with HRF-reactive IgE was able to activate mast cells in vitro. In mouse models of asthma and allergy, Ig-interacting HRF peptides that were shown to block HRF/Ig interactions in vitro inhibited IgE/HRF-induced mast cell activation and in vivo cutaneous anaphylaxis and airway inflammation. Intranasally administered HRF recruited inflammatory immune cells to the lung in naive mice in a mast cell-- and Fc receptor--dependent manner. These results indicate that HRF has a proinflammatory role in asthma and skin immediate hypersensitivity, leading us to suggest HRF as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Human mast cells (MCs) were classified into at least two subtypes, i.e., tryptase- and chymase-positive MCs (MCTC) and tryptase-only-positive MCs (MCT). However, differences in global molecular expression between these subtypes are unknown. Methods: We analyzed public microarray data of MC subtypes derived from various tissues and those of peripheral blood granulocytes by using hierarchical clustering methods to understand the global gene expression profiles. Results: All the transcripts subjected to this clustering analysis were classified into two large clusters, i.e., MC-preferential or granulocyte-preferential. In the original works, MCs from tonsil, lung and skin had been cultured for more than several weeks to obtain highly viable and pure cell populations, and these MCs retained their typical profiles such as intensities of chymase protein expression. Most of the transcripts were commonly expressed by these MC subtypes. However, tonsil-derived MCs and skin-derived MCs but not lung-derived MCs expressed high levels of chymase (CMA1) as expected for the properties of MCTC and MCT. These CMA1-high MCs and CMA1-low MCs respectively expressed distinct sets of transcripts as small gene clusters as well as CMA-1 even after being cultured in the absence of a tissue environment. Conclusions: The MC lineage seems to be far from the granulocyte lineages including basophils. CMA1-high MCs (MCTC) and CMA1-low MCs (MCT) can be regarded as differentiated MC subtypes. As such, importance of data analysis studies will be increasing along with the accumulation of global molecular data in the public database. [ABSTRACT FROM AUTHOR]

Mast cells express high-affinity IgE receptors (FcℇRI) on their surface and can be activated to secrete a variety of biologically active mediators by cross-linking of receptor-bound IgE. Recent studies in animal models indicate that mouse mast cells may play a protective role in host defense against bacteria through the production of tumor necrosis factor-α, mainly as a result of Toll-like receptor (TLR) 4- or CD48-mediated activation. Moreover, several recent observations in animal models have indicated that mast cells may also play a pivotal role in coordinating the early phases of autoimmune diseases, particularly those involving auto-antibodies. We recently identified functional TLR4 and FcγRI on human mast cells, in which their expression had been upregulated by interferon-γ. We compared each of the receptor-mediated gene expression profiles with the FcℇRI-mediated gene expression profile using high-density oligonucleotide probe arrays and discovered that human mast cells may modulate the immune system in a receptor-specific manner. [ABSTRACT FROM AUTHOR]