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  1. Article ; Online: KIT as a master regulator of the mast cell lineage.

    Tsai, Mindy / Valent, Peter / Galli, Stephen J

    The Journal of allergy and clinical immunology

    2022  Volume 149, Issue 6, Page(s) 1845–1854

    Abstract: The discovery in 1987/1988 and 1990 of the cell surface receptor KIT and its ligand, stem cell factor (SCF), was a critical achievement in efforts to understand the development and function of multiple distinct cell lineages. These include hematopoietic ... ...

    Abstract The discovery in 1987/1988 and 1990 of the cell surface receptor KIT and its ligand, stem cell factor (SCF), was a critical achievement in efforts to understand the development and function of multiple distinct cell lineages. These include hematopoietic progenitors, melanocytes, germ cells, and mast cells, which all are significantly affected by loss-of-function mutations of KIT or SCF. Such mutations also influence the development and/or function of additional cells, including those in parts of the central nervous system and the interstitial cells of Cajal (which control gut motility). Many other cells can express KIT constitutively or during immune responses, including dendritic cells, eosinophils, type 2 innate lymphoid cells, and taste cells. Yet the biological importance of KIT in many of these cell types largely remains to be determined. We here review the history of work investigating mice with mutations affecting the white spotting locus (which encodes KIT) or the steel locus (which encodes SCF), focusing especially on the influence of such mutations on mast cells. We also briefly review efforts to target the KIT/SCF pathway with anti-SCF or anti-Kit antibodies in mouse models of allergic disorders, parasite immunity, or fibrosis in which mast cells are thought to play significant roles.
    MeSH term(s) Animals ; Cell Lineage ; Humans ; Immunity, Innate ; Lymphocytes/cytology ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Mast Cells/metabolism ; Mice ; Proto-Oncogene Proteins c-kit/genetics ; Proto-Oncogene Proteins c-kit/metabolism ; Stem Cell Factor/genetics ; Stem Cell Factor/metabolism
    Chemical Substances Stem Cell Factor ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
    Language English
    Publishing date 2022-04-22
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2022.04.012
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  2. Article ; Online: Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns.

    Galli, Stephen J / Gaudenzio, Nicolas / Tsai, Mindy

    Annual review of immunology

    2020  Volume 38, Page(s) 49–77

    Abstract: Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine ... ...

    Abstract Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate
    MeSH term(s) Adaptive Immunity ; Animals ; Biomarkers ; Cytokines/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Humans ; Immunity, Innate ; Inflammation/diagnosis ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation Mediators/metabolism ; Mast Cells/immunology ; Mast Cells/metabolism ; Signal Transduction
    Chemical Substances Biomarkers ; Cytokines ; Inflammation Mediators
    Language English
    Publishing date 2020-05-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 604953-9
    ISSN 1545-3278 ; 0732-0582
    ISSN (online) 1545-3278
    ISSN 0732-0582
    DOI 10.1146/annurev-immunol-071719-094903
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  3. Article ; Online: Legends of Allergy: Stephen J. Galli.

    Tsai, Mindy / Chinthrajah, Sharon / Nadeau, Kari C

    Allergy

    2019  Volume 75, Issue 1, Page(s) 243–245

    MeSH term(s) Allergy and Immunology/history ; History, 20th Century ; History, 21st Century ; Hypersensitivity/history
    Language English
    Publishing date 2019-10-23
    Publishing country Denmark
    Document type Biography ; Historical Article ; News ; Portrait ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.13815
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  4. Article ; Online: Dynamin-related protein 1 differentially regulates FcεRI- and substance P-induced mast cell activation.

    Wang, Ying / Yu, Mang / Matsushita, Kazufumi / Liu, Chen / Ishihara, Naotada / Nomura, Masatoshi / Tsai, Mindy / Galli, Stephen J

    The Journal of allergy and clinical immunology

    2022  Volume 150, Issue 5, Page(s) 1228–1231.e5

    Abstract: Background: The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro, but its functions in MCs activated by various stimuli in vivo have not yet been examined. ...

    Abstract Background: The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro, but its functions in MCs activated by various stimuli in vivo have not yet been examined.
    Objective: We sought to analyze Drp1 function in both mouse and human MCs.
    Methods: We used human peripheral blood-derived cultured MCs and 2 genetic mouse models in which MCs were depleted of Drp1: Drp1
    Results: In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P-stimulated MC activation in vitro and in vivo. This was also true in human peripheral blood-derived cultured MCs in vitro after pharmacologic inhibition of Drp1.
    Conclusion: Drp1 differentially regulates MC activation by various stimuli. Promoting Drp1 activation might therefore represent a novel therapy for suppressing IgE-dependent MC activation. Further, inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P.
    MeSH term(s) Animals ; Humans ; Mice ; Cells, Cultured ; Dynamins/metabolism ; Mast Cells/metabolism ; Receptors, IgE/metabolism ; Substance P/pharmacology ; Substance P/metabolism
    Chemical Substances Dynamins (EC 3.6.5.5) ; Receptors, IgE ; Substance P (33507-63-0) ; DNM1L protein, human (EC 3.6.5.5) ; Dnm1l protein, mouse (EC 3.6.5.5)
    Language English
    Publishing date 2022-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2022.04.028
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  5. Article: Mast cells and IgE in defense against lethality of venoms: Possible "benefit" of allergy[].

    Galli, Stephen J / Metz, Martin / Starkl, Philipp / Marichal, Thomas / Tsai, Mindy

    Allergo journal international

    2020  Volume 29, Issue 2, Page(s) 46–62

    Abstract: Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those ... ...

    Abstract Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, and against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance, and survival, to challenge with reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice surviving an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcεRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances.
    Language English
    Publishing date 2020-03-02
    Publishing country Germany
    Document type Journal Article
    ISSN 2197-0378
    ISSN 2197-0378
    DOI 10.1007/s40629-020-00118-6
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  6. Article ; Online: Mast cells as sources of cytokines, chemokines, and growth factors.

    Mukai, Kaori / Tsai, Mindy / Saito, Hirohisa / Galli, Stephen J

    Immunological reviews

    2018  Volume 282, Issue 1, Page(s) 121–150

    Abstract: Mast cells are hematopoietic cells that reside in virtually all vascularized tissues and that represent potential sources of a wide variety of biologically active secreted products, including diverse cytokines and growth factors. There is strong evidence ...

    Abstract Mast cells are hematopoietic cells that reside in virtually all vascularized tissues and that represent potential sources of a wide variety of biologically active secreted products, including diverse cytokines and growth factors. There is strong evidence for important non-redundant roles of mast cells in many types of innate or adaptive immune responses, including making important contributions to immediate and chronic IgE-associated allergic disorders and enhancing host resistance to certain venoms and parasites. However, mast cells have been proposed to influence many other biological processes, including responses to bacteria and virus, angiogenesis, wound healing, fibrosis, autoimmune and metabolic disorders, and cancer. The potential functions of mast cells in many of these settings is thought to reflect their ability to secrete, upon appropriate activation by a range of immune or non-immune stimuli, a broad spectrum of cytokines (including many chemokines) and growth factors, with potential autocrine, paracrine, local, and systemic effects. In this review, we summarize the evidence indicating which cytokines and growth factors can be produced by various populations of rodent and human mast cells in response to particular immune or non-immune stimuli, and comment on the proven or potential roles of such mast cell products in health and disease.
    MeSH term(s) Animals ; Cell Communication ; Chemokines/metabolism ; Cytokines/metabolism ; Humans ; Hypersensitivity/immunology ; Immunity, Innate ; Mast Cells/immunology
    Chemical Substances Chemokines ; Cytokines
    Language English
    Publishing date 2018-03-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.12634
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  7. Article ; Online: Thirdhand smoke component can exacerbate a mouse asthma model through mast cells.

    Yu, Mang / Mukai, Kaori / Tsai, Mindy / Galli, Stephen J

    The Journal of allergy and clinical immunology

    2018  Volume 142, Issue 5, Page(s) 1618–1627.e9

    Abstract: Background: Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for ...

    Abstract Background: Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for asthma or asthma exacerbation if the disease is already present, how exposure to THS can influence the development or exacerbation of asthma remains unknown.
    Objective: We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a mouse model elicited by means of repeated intranasal challenge with cockroach antigen (CRA).
    Methods: Wild-type mice, α7 nicotinic acetylcholine receptor (nAChR)- or mast cell (MC)-deficient mice, and mice with MCs that lacked α7 nAChRs or were the host's sole source of α7 nAChRs were subjected to epicutaneous NNK exposure, intranasal CRA challenge, or both, and the severity of features of asthma pathology, including airway hyperreactivity, airway inflammation, and airway remodeling, was assessed.
    Results: We found that α7 nAChRs were required to observe adverse effects of epicutaneous NNK exposure on multiple features of CRA-induced asthma pathology. Moreover, MC expression of α7 nAChRs contributed significantly to the ability of epicutaneous NNK exposure to exacerbate airway hyperreactivity to methacholine, airway inflammation, and airway remodeling in this model.
    Conclusion: Our results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a CRA-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.
    MeSH term(s) Administration, Intranasal ; Allergens/administration & dosage ; Animals ; Asthma/immunology ; Cockroaches/immunology ; Cytokines/immunology ; Disease Models, Animal ; Female ; Lung/drug effects ; Lung/immunology ; Mast Cells/drug effects ; Mast Cells/immunology ; Mice, Inbred C57BL ; Mice, Transgenic ; Nitrosamines/toxicity ; Ovalbumin/administration & dosage ; Skin/drug effects ; Skin/immunology ; Smoke/adverse effects ; Tobacco Smoke Pollution ; alpha7 Nicotinic Acetylcholine Receptor/genetics ; alpha7 Nicotinic Acetylcholine Receptor/immunology
    Chemical Substances Allergens ; Cytokines ; Nitrosamines ; Smoke ; Tobacco Smoke Pollution ; alpha7 Nicotinic Acetylcholine Receptor ; 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (7S395EDO61) ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2018-04-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2018.04.001
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  8. Article ; Online: The role of Sp140 revealed in IgE and mast cell responses in Collaborative Cross mice.

    Matsushita, Kazufumi / Li, Xin / Nakamura, Yuki / Dong, Danyue / Mukai, Kaori / Tsai, Mindy / Montgomery, Stephen B / Galli, Stephen J

    JCI insight

    2021  Volume 6, Issue 12

    Abstract: Mouse IgE and mast cell (MC) functions have been studied primarily using inbred strains. Here, we (a) identified effects of genetic background on mouse IgE and MC phenotypes, (b) defined the suitability of various strains for studying IgE and MC ... ...

    Abstract Mouse IgE and mast cell (MC) functions have been studied primarily using inbred strains. Here, we (a) identified effects of genetic background on mouse IgE and MC phenotypes, (b) defined the suitability of various strains for studying IgE and MC functions, and (c) began to study potentially novel genes involved in such functions. We screened 47 Collaborative Cross (CC) strains, as well as C57BL/6J and BALB/cJ mice, for strength of passive cutaneous anaphylaxis (PCA) and responses to the intestinal parasite Strongyloides venezuelensis (S.v.). CC mice exhibited a diversity in PCA strength and S.v. responses. Among strains tested, C57BL/6J and CC027 mice showed, respectively, moderate and uniquely potent MC activity. Quantitative trait locus analysis and RNA sequencing of BM-derived cultured MCs (BMCMCs) from CC027 mice suggested Sp140 as a candidate gene for MC activation. siRNA-mediated knock-down of Sp140 in BMCMCs decreased IgE-dependent histamine release and cytokine production. Our results demonstrated marked variations in IgE and MC activity in vivo, and in responses to S.v., across CC strains. C57BL/6J and CC027 represent useful models for studying MC functions. Additionally, we identified Sp140 as a gene that contributes to IgE-dependent MC activation.
    MeSH term(s) Animals ; Antigens, Nuclear/genetics ; Antigens, Nuclear/immunology ; Collaborative Cross Mice ; Female ; Immunoglobulin E/genetics ; Immunoglobulin E/immunology ; Mast Cells/immunology ; Mast Cells/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Rats ; Rats, Wistar ; Transcription Factors/genetics ; Transcription Factors/immunology
    Chemical Substances Antigens, Nuclear ; Transcription Factors ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2021-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.146572
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  9. Article ; Online: Transcriptome programming of IL-3-dependent bone marrow-derived cultured mast cells by stem cell factor (SCF).

    Wang, Ying / Matsushita, Kazufumi / Jackson, Jennifer / Numata, Takafumi / Zhang, Yue / Zhou, Gao / Tsai, Mindy / Galli, Stephen J

    Allergy

    2021  Volume 76, Issue 7, Page(s) 2288–2291

    MeSH term(s) Bone Marrow ; Bone Marrow Cells ; Cells, Cultured ; Humans ; Interleukin-3/genetics ; Mast Cells ; Stem Cell Factor/genetics ; Transcriptome
    Chemical Substances Interleukin-3 ; Stem Cell Factor
    Language English
    Publishing date 2021-03-24
    Publishing country Denmark
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.14808
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  10. Article ; Online: Development of multiple features of antigen-induced asthma pathology in a new strain of mast cell deficient BALB/c-Kit

    Hernandez, Joseph D / Yu, Mang / Sibilano, Riccardo / Tsai, Mindy / Galli, Stephen J

    Laboratory investigation; a journal of technical methods and pathology

    2019  Volume 100, Issue 4, Page(s) 516–526

    Abstract: Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of ... ...

    Abstract Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the Kit
    MeSH term(s) Animals ; Asthma/chemically induced ; Asthma/pathology ; Asthma/physiopathology ; Disease Models, Animal ; Mast Cells/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Proto-Oncogene Proteins c-kit/genetics
    Chemical Substances Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
    Language English
    Publishing date 2019-12-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1038/s41374-019-0354-2
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