Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation

Siegel, Andrea; Stone, Kelly D.; Cruse, Glenn; Lawrence, Monica G.; Olivera, Ana; Jung, Mi‐Yeon; Barber, John S.; Freeman, Alexandra F.; Holland, Steven M.; O’Brien, Michelle; Jones, Nina; Wisch, Laura; Kong, Heidi H.; Desai, Avanti; Farber, Orly N.; Gilfillan, Alasdair M.; Rivera, Juan; Milner, Joshua D.

doi:10.1016/j.jaci.2013.08.045

Cited by 108 publications

(111 citation statements)

References 32 publications

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“…IgE düzeyinde artışa neden olan mekanizma tam olarak aydınlatılmamış olsa da uygunsuz IL4 üretimi sorumlu tutulmuştur (37). Yüksek serum IgE düzeylerine rağmen klinik olarak allerjik hastalık varlığı ve anaflaksi oldukça nadirdir (13,(38)(39)(40). Benzer şekilde bizim olgularımızdan STAT3 gen mutasyonu taşıyanlarda allerjene duyarlanma saptanmamıştır.…”

Section: Discussionunclassified

“…Ancak yeni çalışmalarda bunun aksini gösteren veriler de elde edilmiştir. Amerikan Ulusal Sağlık Enstitüsü (NIH; National Institute of Health) tarafından yürütülen 71 otozomal baskın HİES tanılı hasta serisinde %40'lara varan oranda gıda ilişki hipersensitivite reaksiyonu ve %8.5 oranında gıda ilişkili anaflaksi tanımlanmıştır (13). Kontrol grubu olarak alınan benzer serum IgE düzeylerine sahip (ortanca serum IgE değeri 7079 IU/ml) atopik dermatit tanılı hastalarda ise gıda ilişkili aşırı duyarlılık %58 ve anaflaksi %33 bulunmuştur.…”

Section: Discussionunclassified

“…Kontrol grubu olarak alınan benzer serum IgE düzeylerine sahip (ortanca serum IgE değeri 7079 IU/ml) atopik dermatit tanılı hastalarda ise gıda ilişkili aşırı duyarlılık %58 ve anaflaksi %33 bulunmuştur. Bu durumda sadece duyarlanma varlığına bakılarak bu iki hastalığı ayırt etmek mümkün olmayabilir (13). Yenidoğan döneminde egzematöz döküntü ve stafilokoksik deri enfeksiyonları STAT3 için klasik bulgu olmakla beraber tanı yaşı ortalama 6.8 yıldır (41).…”

Section: Discussionunclassified

“…STAT3 gen defektinde IgE ve eozinofil yüksekliğine rağmen klasik olarak allerjik hastalık nadir görülür. Buna neden olarak mast hücre degranülasyonu ve IgE-bazofil bağlanması sırasında STAT3 sinyal yolağına gereksinim gösterilmiştir (13). Ancak anaflaksi ve allerjik hastalık bildirilen olgular da literatürde mevcuttur (13,14).…”

Section: Introductionunclassified

“…Buna neden olarak mast hücre degranülasyonu ve IgE-bazofil bağlanması sırasında STAT3 sinyal yolağına gereksinim gösterilmiştir (13). Ancak anaflaksi ve allerjik hastalık bildirilen olgular da literatürde mevcuttur (13,14). Bununla beraber DOCK8 gen defekti olan hastalarda inek sütü başta olmak üzere gıda allerjileri sık görülmektedir (15,16).…”

Section: Introductionunclassified

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Serum IgE Düzeyi ve Eozinofil Sayısı ile Atopik Hastalıklar Hiper IgE Sendromu’ndan Ayırt Edilebilir mi?

Kıykım¹,

Yüce²,

Baris³

et al. 2017

Asthma Allergy Immunol

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Section: Discussionunclassified

Section: Introductionunclassified

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Serum IgE Düzeyi ve Eozinofil Sayısı ile Atopik Hastalıklar Hiper IgE Sendromu’ndan Ayırt Edilebilir mi?

Kıykım¹,

Yüce²,

Baris³

et al. 2017

Asthma Allergy Immunol

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Mast cell activation: A complex interplay of positive and negative signaling pathways

Sibilano¹,

2014

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Mast cells regulate the immunological responses causing allergy and autoimmunity, and contribute to the tumor microenvironment through generation and secretion of a broad array of preformed, granule-stored and de novo synthesized bioactive compounds. The release and production of mast cell mediators is the result of a coordinated signaling machinery, followed by the FcεRI and FcγR antigen ligation. In this review, we present the latest understanding of FcεRI and FcγR signaling, required for the canonical mast cell activation during allergic responses and anaphylaxis. We then describe the cooperation between the signaling of FcR and other recently characterized membrane-bound receptors (i.e., IL-33R and thymic stromal lymphopoietin receptor) and their role in the chronic settings, where mast cell activation is crucial for the development and the sustainment of chronic diseases, such as asthma or airway inflammation. Finally, we report how the FcR activation could be used as a therapeutic approach to treat allergic and atopic diseases by mast cell inactivation. Understanding the magnitude and the complexity of mast cell signaling is necessary to identify the mechanisms underlying the potential effector and regulatory roles of mast cells in the biology and pathology of those disease settings in which mast cells are activated.Keywords: FcεRI r FcγR r IL-33 r mast cells r TSLP IntroductionMast cells originate in the BM from a lineage-specific multipotent hematopoietic progenitor, circulate as CD34 + precursors until they migrate to tissues and mature into effector cells in the proximity of organs and blood vessels. Mast cells respond to antigenic stimulation through the cross-linking of immunoglobulin E (IgE) bound to high-affinity receptors for IgE (FcεRI) and the activation of the FcγR after IgG binding (reviewed in [1,2]). Upon activation, mast cells release either preformed, granule-stored mediators, such as histamine and proteases, or newly generated mediators, such as eicosanoids, cytokines, and chemokines [3]. Although the basic molecular mechanisms of Ig:Fc activation have been extensively studied in the past 15 years [4][5][6], new molecules regulating the Correspondence: Dr. Barbara Frossi e-mail: barbara.frossi@uniud.it FcR-signaling cascades have recently been characterized, suggesting not only a still vivid interest in the field of mast cell activation and signaling, but also in identifying putative new therapeutic targets for intervention in mast cell dependent disorders. This review will focus on three aspects of mast cell activation/function. First, we give an essential but complete overview of the FcR-mediated activation in mast cells and report on recent advances in IgE-and IgG-mediated signaling. For clarity, we will dissect and analyze the signals derived from each pathway, with particular attention to the newly identified positive or negative molecular players describing -when possible -their implication toward degranulation and cytokine production. Second, we highlight the growing interest aroun...

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Cannabidiol Inhibits IgE‐Mediated Mast Cell Degranulation and Anaphylaxis in Mice

Yang,

Lee,

Kim

et al. 2023

Molecular Nutrition Food Res

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ScopeCannabidiol (CBD), the most abundant non‐psychoactive constituent of the plant Cannabis sativa, is known to possess immune modulatory properties. This study investigates the effects of CBD on mast cell degranulation in human and mouse primary mast cells and passive cutaneous anaphylaxis in mice.Methods and resultsMouse bone marrow‐derived mast cells and human cord‐blood derived mast cells are generated. CBD suppressed antigen‐stimulated mast cell degranulation in a concentration‐dependent manner. Mechanistically, CBD inhibited both the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization in mast cells, while exerting no effect on FcεRI expression and IgE binding to FcεRI. These suppressive effects are preserved in the mast cells that are depleted of type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as in the presence of CB1 agonist, CB2 agonist, CB1 inverse agonist, and CB2 inverse agonist. CBD also inhibited the development of mast cells in a long‐term culture. The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells.ConclusionBased on these results, the administration of CBD is a new therapeutic intervention in mast cell‐associated anaphylactic diseases.

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Diminished allergic disease in patients with STAT3 mutations reveals a role for STAT3 signaling in mast cell degranulation

Cited by 108 publications

References 32 publications

Serum IgE Düzeyi ve Eozinofil Sayısı ile Atopik Hastalıklar Hiper IgE Sendromu’ndan Ayırt Edilebilir mi?

Serum IgE Düzeyi ve Eozinofil Sayısı ile Atopik Hastalıklar Hiper IgE Sendromu’ndan Ayırt Edilebilir mi?

Mast cell activation: A complex interplay of positive and negative signaling pathways

Cannabidiol Inhibits IgE‐Mediated Mast Cell Degranulation and Anaphylaxis in Mice

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