Article
Immunology
Monica Thapaliya, Hydar Ali
Summary: This article investigates the role of GRK2 in mouse mast cells. It is found that GRK2 inhibits the responses mediated by MRGPRX2/B2 for C48/80 and SP, but not for LL-37. It is also discovered that GRK2 plays a role in IgE-mediated PCA and itch, but not in PSA.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Chalatip Chompunud Na Ayudhya, Aetas Amponnawarat, Saptarshi Roy, Carole A. Oskeritzian, Hydar Ali
Summary: The study found that rocuronium induces degranulation in human MCs via the receptor MRGPRX2, indicating a more complex mechanism of perioperative hypersensitivity than previously thought due to differences between MRGPRX2 and MrgprB2, and the lack of enhanced response in cells expressing MRGPRX2 variants.
Article
Immunology
Aetas Amponnawarat, Chalatip Chompunud Na Ayudhya, Hydar Ali
Summary: Pseudomonas aeruginosa infections are difficult to treat due to biofilm formation and antibiotic resistance, but a lipidated HDP mimetic called murepavadin has shown antibacterial activity against multi-drug-resistant strains. Murepavadin activates human MCs via MRGPRX2 and murine MCs via MrgprB2, potentially contributing to bacterial clearance and wound healing.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medical Laboratory Technology
Didier G. Ebo, Kevin Heremans, Michiel Beyens, Marie-Line M. van der Poorten, Athina L. Van Gasse, Christel Mertens, Michel Van Houdt, Vito Sabato, Jessy Elst
Summary: The basophil activation test (BAT) is a reliable complementary diagnostic for IgE-dependent allergies, but it has limitations. In contrast, the mast cell activation test (MAT) using passively sensitized mast cells (MCs) has advantages such as using frozen serum samples and studying IgE-independent mechanisms.
CLINICA CHIMICA ACTA
(2022)
Article
Immunology
Monica Thapaliya, Aetas Amponnawarat, John J. G. Tesmer, Hydar Ali
Summary: Research has shown that GRK2 inhibitors paroxetine and CCG258747 can effectively modulate MC responses mediated by IgE, reducing allergic reactions and enhancing cutaneous host defense.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chalatip Chompunud Na Ayudhya, Aetas Amponnawarat, Hydar Ali
Summary: The neuropeptide substance P activates mast cells through MrgprB2, contributing to neurogenic inflammation and pain in atopic dermatitis. Certain MRGPRX2 agonists lead to beta-arrestin recruitment, revealing a new pathway for receptor internalization and desensitization. The study highlights a tyrosine residue in the highly conserved NPxxY motif of MRGPRX2 that plays a role in both G protein- and beta-arrestin-mediated responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Alessandro Toscano, Jessy Elst, Athina L. Van Gasse, Michiel Beyens, Marie-Line van der Poorten, Chris H. Bridts, Christel Mertens, Michel Van Houdt, Margo M. Hagendorens, Samuel Van Remoortel, Jean-Pierre Timmermans, Didier G. Ebo, Vito Sabato
Summary: This study explored the expression and functionality of MRGPRX2 in and on basophils. The results showed that basophils barely express MRGPRX2 in resting conditions, but it can be quickly upregulated after stimulation and make cells responsive to MRGPRX2 occupation. These findings provide a model for studying MRGPRX2 agonism or antagonism and the mechanisms associated with IDHRs.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Zhao Wang, Xi Zhao, Hongmei Zhou, Delu Che, Xiaojie Du, Dan Ye, Weihui Zeng, Songmei Geng
Summary: Mast cell activation is associated with the pathogenesis of various immune dysregulatory skin disorders. Recent studies have shown that the activation of an IgE-independent pseudo-allergic route is mainly mediated through Mas-Related G protein-coupled receptor X2 (MRGPRX2) and regulated by Ryanodine receptor (RYR). This finding provides insights into the role of RYR in MRGPRX2-mediated pseudo-allergic dermatitis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Maram Bawazir, Aetas Amponnawarat, Yvonne Hui, Carole A. Oskeritzian, Hydar Ali
Summary: The MRGPRX2 receptor plays a role in hypersensitivity reactions and cutaneous conditions. The MRGPRX2 agonist C9 has shown potential in modulating MC-mediated disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Patrycja Kwiecinska, Mateusz Kwitniewski, Kamila Kwiecien, Agnieszka Morytko, Pawel Majewski, Natalia Pocalun, Maciej Pastuszczak, Marcin Migaczewski, Joanna Cichy, Beata Grygier
Summary: This study investigated the role of secretory leukocyte protease inhibitor (SLPI) in mast cell-dependent processes and found that SLPI inhibits the activity of chymase in mast cells and enhances their degranulation. The study also showed that SLPI is expressed in dermal mast cells of patients with psoriasis. These findings reveal previously unknown mechanisms underlying FceRI and Mrgprb2-dependent mast cell function.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Nisha Adhikari, Won-Sik Shim
Summary: The study found that caffeic acid phenethyl ester (CAPE) can inhibit the activation of MRGPRX2/MrgprB2 induced by C48/80, and inhibits mouse peritoneal mast cell degranulation in both IgE-dependent and MrgprB2-dependent manners. These data suggest that CAPE can suppress pseudo-allergic reactions evoked by C48/80 via MrgprB2-dependent pathway.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Didier G. Ebo, Michiel Beyens, Kevin Heremans, Marie-Line M. van der Poorten, Athina L. Van Gasse, Christel Mertens, Michel Van Houdt, Vito Sabato, Jessy Elst
Summary: Immediate hypersensitivity reactions are challenging to diagnose due to their wide range of clinical presentations and uncertain mechanisms. These reactions can be caused by activation and degranulation of specific and nonspecific mast cells and basophils. Degranulation of these cells leads to the release of inflammatory mediators, which can vary depending on the trigger.
CURRENT PHARMACEUTICAL DESIGN
(2023)
Article
Pharmacology & Pharmacy
Nan Wang, Jue Wang, Yongjing Zhang, Yingnan Zeng, Shiling Hu, Haoyun Bai, Yajing Hou, Cheng Wang, Huaizhen He, Langchong He
Summary: The study revealed that IMP can reduce SP-induced calcium flux and suppress MC degranulation. IMP can alleviate SP-induced mouse PCA and ASA, and mitigate lung inflammation in an OVA-induced asthma model by inhibitiing MC activation in lung tissue. Additionally, IMP binds well to MRGPRX2 protein, suggesting it is a novel inhibitor for treating allergic asthma.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Allergy
Kazufumi Kunimura, Sayaka Akiyoshi, Takehito Uruno, Keisuke Matsubara, Daiji Sakata, Kenji Morino, Kenichiro Hirotani, Yoshinori Fukui
Summary: This study reveals the role of DOCK2 in MRGPRX2/B2-mediated MC degranulation and anaphylaxis. The results show that MRGPRB2-mediated Rac activation and PAK1 phosphorylation were impaired in DOCK2-deficient MCs, leading to severe attenuation of MC degranulation and anaphylaxis.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Allergy
Didier G. Ebo, Nils Vlaeminck, Marie-Line M. van der Poorten, Jessy Elst, Alessandro Toscano, Athina L. Van Gasse, Margo M. Hagendorens, Sophie Aerts, Ine Adriaensens, Vera Saldien, Vito Sabato
Summary: Perioperative hypersensitivity is an important health issue, and misdiagnosis can have serious consequences. However, the correct diagnosis is not always straightforward due to incorrect nomenclature, lack of accessible in-vitro/ex-vivo tests, and uncertainties regarding non-irritating skin test concentrations. In this editorial, we provide a summary of the key findings and insights from 25 years of research on the mechanisms, diagnosis, and management of perioperative hypersensitivity.
WORLD ALLERGY ORGANIZATION JOURNAL
(2023)
Article
Gastroenterology & Hepatology
Benjamin L. Wright, Nielsen Q. Fernandez-Becker, Neeraja Kambham, Natasha Purington, Shu Cao, Dana Tupa, Wenming Zhang, Sayantani B. Sindher, Matthew A. Rank, Hirohito Kita, David A. Katzka, Kelly P. Shim, Bryan J. Bunning, Alfred D. Doyle, Elizabeth A. Jacobsen, Mindy Tsai, Scott D. Boyd, Monali Manohar, R. Sharon Chinthrajah
Summary: In this pilot study, peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Allergy
Lucy Duan, Alper Celik, Jennifer A. Hoang, Klara Schmidthaler, Delvin So, Xiaojun Yin, Christina M. Ditlof, Marta Ponce, Julia E. M. Upton, Jean-Soo Lee, Lisa Hung, Heimo Breiteneder, Chiara Palladino, Adelle R. Atkinson, Vy H. D. Kim, Alireza Berenjy, Maria Asper, David Hummel, Samantha Wong, Mara Alexanian-Farr, Ahuva Magder, Sharon R. Chinthrajah, Kaori Mukai, Mindy Tsai, Kari Nadeau, Stephen J. Galli, Arun K. Ramani, Zsolt Szepfalusi, Thomas Eiwegger
Summary: The basophil activation test (BAT) can effectively diagnose peanut and tree nut allergies, reducing the need for high-risk OFCs in multi-nut-sensitized children.
Review
Dermatology
Auriane Corbiere, Alexia Loste, Nicolas Gaudenzio
Summary: Mast cells are innate immune cells that play a crucial role in protecting the host against environmental threats and allergic diseases. Recent studies have shown that mast cells regulate skin inflammation and pain and itch sensations through the signaling of Mas-related G protein-coupled receptors. Activation of mast cells can lead to the release of various substances that modulate vascular permeability and immune responses.
EXPERIMENTAL DERMATOLOGY
(2021)
Letter
Allergy
Ying Wang, Kazufumi Matsushita, Jennifer Jackson, Takafumi Numata, Yue Zhang, Gao Zhou, Mindy Tsai, Stephen J. Galli
Article
Immunology
Anais Wanet, Mahmoud A. Bassal, Sweta B. Patel, Francisco Marchi, Samanta A. Mariani, Nouraiz Ahmed, Haoran Zhang, Marta Borchiellini, Sisi Chen, Junyan Zhang, Annalisa Di Ruscio, Kensuke Miyake, Mindy Tsai, Anuya Paranjape, Shin-Young Park, Hajime Karasuyama, Timm Schroeder, Elaine Dzierzak, Stephen J. Galli, Daniel G. Tenen, Robert S. Welner
Summary: E-cadherin expression in the hematopoietic system was studied using single-cell RNA-sequencing analyses and immunophenotyping. High levels of E-cadherin were found in progenitors within the granulocyte-monocyte progenitors (GMPs) fraction, with an enriched capacity to differentiate into basophils and mast cells. The transcriptional priming of these progenitors to the basophil and mast cell lineages was observed, with GATA-2 directly regulating E-cadherin expression in these lineages.
SCIENCE IMMUNOLOGY
(2021)
Article
Allergy
Philipp Starkl, Nicolas Gaudenzio, Thomas Marichal, Laurent L. Reber, Riccardo Sibilano, Martin L. Watzenboeck, Frederic Fontaine, Andre C. Mueller, Mindy Tsai, Sylvia Knapp, Stephen J. Galli
Summary: The study found that IgE sensitization enhances MC detoxification of honeybee venom by promoting proteolytic degradation and heparin-related interference with toxicity. This research emphasizes the importance of IgE, MCs, and specific MC products in defense against honeybee venom.
Editorial Material
Multidisciplinary Sciences
Jasper B. J. Kamphuis, William P. M. Worrall, Julien Stackowicz, Aurelie Mougel, Emilie Maure, Eva Conde, Pierre Bruhns, Laurent Guilleminault, Nicolas Gaudenzio, Jinmiao Chen, Rebecca Gentek, Laurent L. Reber
Summary: The researchers found that interleukin-33 can induce accumulation of tumor-associated macrophages expressing the Fc epsilon RI receptor, but raised concerns about the specificity of the anti-Fc epsilon RI antibody used in the study.
Article
Immunology
Julien Stackowicz, Nicolas Gaudenzio, Nadine Serhan, Eva Conde, Ophelie Godon, Thomas Marichal, Philipp Starkl, Bianca Balbino, Axel Roers, Pierre Bruhns, Friederike Jonsson, Philippe Moguelet, Sophie Georgin-Lavialle, Lori Broderick, Hal M. Hoffman, Stephen J. Galli, Laurent L. Reber
Summary: Gain-of-function mutations in NLRP3 gene cause CAPS, with neutrophils potentially being the main cellular drivers of CAPS pathology.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Kazufumi Matsushita, Xin Li, Yuki Nakamura, Danyue Dong, Kaori Mukai, Mindy Tsai, Stephen B. Montgomery, Stephen J. Galli
Summary: By studying 47 CC strains, we identified significant variations in IgE and MC activity in vivo, C57BL/6J and CC027 were found to be effective models for studying MC functions, and Sp140 was identified as a gene contributing to IgE-dependent MC activation.
Article
Medicine, General & Internal
Christopher Michael Warren, Theo Thomas Snow, Alexandra S. Lee, Mihir Mukesh Shah, Anja Heider, Andra Blomkalns, Brooke Betts, Anthony S. Buzzanco, Joseph Gonzalez, R. Sharon Chinthrajah, Evan Do, Iris Chang, Diane Dunham, Grace Lee, Ruth O'Hara, Helen Park, Mohamed H. Shamji, Lisa Schilling, Sayantani B. Sindher, Deepak Sisodiya, Eric Smith, Mindy Tsai, Stephen J. Galli, Cezmi Akdis, Kari C. Nadeau
Summary: This study analyzed 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines, indicating a potential non-IgE mediated immune response to PEG in most individuals. Women and those with a history of allergic reactions may have an elevated risk of mRNA vaccine allergy.
Review
Immunology
Marie Tauber, Fang Wang, Brian Kim, Nicolas Gaudenzio
Summary: Peripheral neurons play a crucial role in transmitting sensations and regulating type 2 immune responses and allergic inflammation. Neurons can express receptors previously thought to be exclusive to the immune system, and interact with immune cells to modulate their activation status during allergic inflammation.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Review
Allergy
Mindy Tsai, Peter Valent, Stephen J. Galli
Summary: The discovery of the cell surface receptor KIT and its ligand, stem cell factor (SCF), in 1987/1988 and 1990 has greatly contributed to our understanding of the development and function of various cell lineages. Mutations in KIT or SCF can have significant effects on the development and/or function of hematopoietic progenitors, melanocytes, germ cells, and mast cells. The biological importance of KIT in other cell types is still not well understood.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Allergy
Nicolas Castano, Kaiser Chua, Abhinav Kaushik, Sungu Kim, Seth C. Cordts, Ceena D. Nafarzadegan, Grady H. Hofmann, Hana Seastedt, Jackson P. Schuetz, Diane Dunham, Ella S. Parsons, Mindy Tsai, Shu Cao, Manisha Desai, Sayantani B. Sindher, R. Sharon Chinthrajah, Stephen J. Galli, Kari C. Nadeau, Sindy K. Y. Tang
Summary: Avidin and CD63 have been found to be reliable basophil activation markers that enhance the identification of activated basophils and improve the classification accuracy of peanut allergy.
Article
Biochemical Research Methods
Nora Vivanco Gonzalez, John-Paul Oliveria, Dmitry Tebaykin, Geoffrey T. Ivison, Kaori Mukai, Mindy M. Tsai, Luciene Borges, Kari C. Nadeau, Stephen J. Galli, Albert G. Tsai, Sean C. Bendall
Summary: This study utilized mass cytometry to capture distinct phenotypes of granulocytes, and through optimized protocols, achieved in-depth characterization of basophils, eosinophils, and neutrophils. This research is of great significance for understanding the roles of granulocytes in homeostasis and immune activation.
Meeting Abstract
Allergy
Sharon Chinthrajah, Shu Cao, Mindy Tsai, Kaori Mukai, Robert Tibshirani, Sayantani Sindher, Kari Nadeau, Stephen Galli
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)