Full Text Journal Articles by
Author Mark C Siracusa

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Tumor suppressor p53 regulates intestinal type 2 immunity.

Chun-Yuan Chang, Jianming Wang, Yuhan Zhao, Juan Liu, Xue Yang, Xuetian Yue, Huaying Wang, Fan Zhou, Juan M Inclan-Rico, John J Ponessa, Ping Xie, Lanjing Zhang, Mark C Siracusa, Zhaohui Feng, Wenwei Hu,

The role of p53 in tumor suppression has been extensively studied and well-established. However, the role of p53 in parasitic infections and the intestinal type 2 immunity is unclear. Here, we report that p53 is crucial for intestinal type 2 immunity in response to the infection of parasites, such as ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):3371]

Cited: 0 times

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Editorial: Recent Advances in the Immunology of Helminth Infection - Protection, Pathogenesis and Panaceas.

Kara J Filbey, Constance A M Finney, Paul R Giacomin, Mark C Siracusa,

Front Immunol (Frontiers in immunology)
[2021, 12:663753]

Cited: 0 times

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Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition.

Juan M Inclan-Rico, John J Ponessa, Nuriban Valero-Pacheco, Christina M Hernandez, Chandler B Sy, Alexander D Lemenze, Aimee M Beaulieu, Mark C Siracusa,

Type 2 cytokine responses promote parasitic immunity and initiate tissue repair; however, they can also result in immunopathologies when not properly restricted. Although basophilia is recognized as a common feature of type 2 inflammation, the roles basophils play in regulating these responses are unknown. Here, we demonstrate that helminth-induced group ... Read more >>

Nat Immunol (Nature immunology)
[2020, 21(10):1181-1193]

Cited: 6 times

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Trichinella spiralis-induced mastocytosis and erythropoiesis are simultaneously supported by a bipotent mast cell/erythrocyte precursor cell.

Juan M Inclan-Rico, Christina M Hernandez, Everett K Henry, Hannah G Federman, Chandler B Sy, John J Ponessa, Alexander D Lemenze, Nathanael Joseph, Patricia Soteropoulos, Aimee M Beaulieu, George S Yap, Mark C Siracusa,

Anti-helminth responses require robust type 2 cytokine production that simultaneously promotes worm expulsion and initiates the resolution of helminth-induced wounds and hemorrhaging. However, how infection-induced changes in hematopoiesis contribute to these seemingly distinct processes remains unknown. Recent studies have suggested the existence of a hematopoietic progenitor with dual mast cell-erythrocyte ... Read more >>

PLoS Pathog (PLoS pathogens)
[2020, 16(5):e1008579]

Cited: 2 times

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The Transcription Factor PLZF Is Necessary for the Development and Function of Mouse Basophils.

Sai Zhang, Joshua A Vieth, Agata Krzyzanowska, Everett K Henry, Lisa K Denzin, Mark C Siracusa, Derek B Sant'Angelo,

Basophils are innate immune cells associated with type 2 immunity, allergic reactions, and host defense against parasite infections. In this study, we show that the transcription factor PLZF, which is known for its essential role in the function and development of several innate lymphocyte subsets, is also important for the ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2019, 203(5):1230-1241]

Cited: 0 times

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Contributions of innate lymphocytes to allergic responses.

Juan M Inclan-Rico, John J Ponessa, Mark C Siracusa,

<h4>Purpose of review</h4>Allergic diseases represent a growing global health concern, especially among pediatric populations. Current strategies for the treatment of allergies and asthma focus on limiting the severity of the symptoms; however, additional research investigating the mechanisms promoting inflammation in the context of allergic reactions may lead to the development ... Read more >>

Curr Opin Allergy Clin Immunol (Current opinion in allergy and clinical immunology)
[2019, 19(2):175-184]

Cited: 0 times

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Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44.

Meimei Shan, Jorge Carrillo, Ada Yeste, Cindy Gutzeit, Daniel Segura-Garzón, A Cooper Walland, Marc Pybus, Emilie K Grasset, John R Yeiser, Dean B Matthews, Willem van de Veen, Laura Comerma, Bing He, Tadech Boonpiyathad, Haekyung Lee, Julià Blanco, Lisa C Osborne, Mark C Siracusa, Mübeccel Akdis, David Artis, Saurabh Mehandru, Hugh A Sampson, M Cecilia Berin, Kang Chen, Andrea Cerutti,

B cells thwart antigenic aggressions by releasing immunoglobulin M (IgM), IgG, IgA, and IgE, which deploy well-understood effector functions. In contrast, the role of secreted IgD remains mysterious. We found that some B cells generated IgD-secreting plasma cells following early exposure to external soluble antigens such as food proteins. Secreted IgD ... Read more >>

Immunity (Immunity)
[2018, 49(4):709-724.e8]

Cited: 16 times

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First Responders: Innate Immunity to Helminths.

Juan M Inclan-Rico, Mark C Siracusa,

Helminth infections represent a significant public health concern resulting in devastating morbidity and economic consequences across the globe. Helminths migrate through mucosal sites causing tissue damage and the induction of type 2 immune responses. Antihelminth protection relies on the mobilization and activation of multiple immune cells, including type 2 innate ... Read more >>

Trends Parasitol (Trends in parasitology)
[2018, 34(10):861-880]

Cited: 19 times

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Type 2 cytokine responses: regulating immunity to helminth parasites and allergic inflammation.

Everett K Henry, Juan M Inclan-Rico, Mark C Siracusa,

Purpose of Review:It is well established that T helper type 2 (TH2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding ... Read more >>

Curr Pharmacol Rep (Current pharmacology reports)
[2017, 3(6):346-359]

Cited: 9 times

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Skin-derived TSLP systemically expands regulatory T cells.

Theresa M Leichner, Atsushi Satake, Victor Sanoe Harrison, Yukinori Tanaka, Angela S Archambault, Brian S Kim, Mark C Siracusa, Warren J Leonard, Ali Naji, Gregory F Wu, David Artis, Taku Kambayashi,

Regulatory T cells (Tregs) are a subset of CD4<sup>+</sup> T cells with suppressive function and are critical for limiting inappropriate activation of T cells. Hence, the expansion of Tregs is an attractive strategy for the treatment of autoimmune diseases. Here, we demonstrate that the skin possesses the remarkable capacity to ... Read more >>

J Autoimmun (Journal of autoimmunity)
[2017, 79:39-52]

Cited: 4 times

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The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation.

Chandler B Sy, Mark C Siracusa,

Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, ... Read more >>

Front Physiol (Frontiers in physiology)
[2016, 7:214]

Cited: 6 times

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Innate cell communication kick-starts pathogen-specific immunity.

Amariliz Rivera, Mark C Siracusa, George S Yap, William C Gause,

Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, ... Read more >>

Nat Immunol (Nature immunology)
[2016, 17(4):356-363]

Cited: 89 times

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IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing.

Gregory D Rak, Lisa C Osborne, Mark C Siracusa, Brian S Kim, Kelvin Wang, Ardeshir Bayat, David Artis, Susan W Volk,

Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung, and gut, and promote proinflammatory or epithelial repair functions after ... Read more >>

J Invest Dermatol (The Journal of investigative dermatology)
[2016, 136(2):487-496]

Cited: 88 times

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Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity.

Paul R Giacomin, Ryan H Moy, Mario Noti, Lisa C Osborne, Mark C Siracusa, Theresa Alenghat, Bigang Liu, Kelly A McCorkell, Amy E Troy, Gregory D Rak, Yinling Hu, Michael J May, Hak-Ling Ma, Lynette A Fouser, Gregory F Sonnenberg, David Artis,

Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)-specific deletions in either inhibitor of κB kinase (IKK)α or IKKβ, two critical regulators of NFκB activation, we demonstrate ... Read more >>

J Exp Med (The Journal of experimental medicine)
[2015, 212(10):1513-1528]

Cited: 43 times

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Basophils promote innate lymphoid cell responses in inflamed skin.

Brian S Kim, Kelvin Wang, Mark C Siracusa, Steven A Saenz, Jonathan R Brestoff, Laurel A Monticelli, Mario Noti, Elia D Tait Wojno, Thomas C Fung, Masato Kubo, David Artis,

Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2014, 193(7):3717-3725]

Cited: 107 times

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Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation.

Lisa C Osborne, Laurel A Monticelli, Timothy J Nice, Tara E Sutherland, Mark C Siracusa, Matthew R Hepworth, Vesselin T Tomov, Dmytro Kobuley, Sara V Tran, Kyle Bittinger, Aubrey G Bailey, Alice L Laughlin, Jean-Luc Boucher, E John Wherry, Frederic D Bushman, Judith E Allen, Herbert W Virgin, David Artis,

The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this ... Read more >>

Science (Science (New York, N.Y.))
[2014, 345(6196):578-582]

Cited: 142 times

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Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.

Mark C Siracusa, Steven A Saenz, Elia D Tait Wojno, Brian S Kim, Lisa C Osborne, Carly G Ziegler, Alain J Benitez, Kathryn R Ruymann, Donna L Farber, Patrick M Sleiman, Hakon Hakonarson, Antonella Cianferoni, Mei-Lun Wang, Jonathan M Spergel, Michael R Comeau, David Artis,

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we ... Read more >>

Immunity (Immunity)
[2013, 39(6):1158-1170]

Cited: 41 times

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IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells.

Steven A Saenz, Mark C Siracusa, Laurel A Monticelli, Carly G K Ziegler, Brian S Kim, Jonathan R Brestoff, Lance W Peterson, E John Wherry, Ananda W Goldrath, Avinash Bhandoola, David Artis,

The predominantly epithelial cell-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) can promote CD4(+) Th2 cell-dependent immunity, inflammation, and tissue repair at barrier surfaces through the induction of multiple innate immune cell populations. IL-25 and IL-33 were previously shown to elicit four innate cell populations, named natural helper cells, ... Read more >>

J Exp Med (The Journal of experimental medicine)
[2013, 210(9):1823-1837]

Cited: 78 times

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Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.

Mario Noti, Brian S Kim, Mark C Siracusa, Gregory D Rak, Masato Kubo, Amin E Moghaddam, Quentin A Sattentau, Michael R Comeau, Jonathan M Spergel, David Artis,

<h4>Background</h4>Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy.<h4>Objective</h4>We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy.<h4>Methods</h4>Mice were epicutaneously sensitized with ovalbumin or peanut on an ... Read more >>

J Allergy Clin Immunol (The Journal of allergy and clinical immunology)
[2014, 133(5):1390-9, 1399.e1-6]

Cited: 116 times

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Basophils and allergic inflammation.

Mark C Siracusa, Brian S Kim, Jonathan M Spergel, David Artis,

Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in human subjects and murine systems ... Read more >>

J Allergy Clin Immunol (The Journal of allergy and clinical immunology)
[2013, 132(4):789-801; quiz 788]

Cited: 105 times

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TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation.

Brian S Kim, Mark C Siracusa, Steven A Saenz, Mario Noti, Laurel A Monticelli, Gregory F Sonnenberg, Matthew R Hepworth, Abby S Van Voorhees, Michael R Comeau, David Artis,

Innate lymphoid cells (ILCs) are a recently identified family of heterogeneous immune cells that can be divided into three groups based on their differential developmental requirements and expression of effector cytokines. Among these, group 2 ILCs produce the type 2 cytokines interleukin-5 (IL-5) and IL-13 and promote type 2 inflammation ... Read more >>

Sci Transl Med (Science translational medicine)
[2013, 5(170):170ra16]

Cited: 298 times

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Thymic stromal lymphopoietin-dependent basophils promote Th2 cytokine responses following intestinal helminth infection.

Paul R Giacomin, Mark C Siracusa, Kevin P Walsh, Richard K Grencis, Masato Kubo, Michael R Comeau, David Artis,

CD4(+) Th2 cytokine responses promote the development of allergic inflammation and are critical for immunity to parasitic helminth infection. Recent studies highlighted that basophils can promote Th2 cytokine-mediated inflammation and that phenotypic and functional heterogeneity exists between classical IL-3-elicited basophils and thymic stromal lymphopoietin (TSLP)-elicited basophils. However, whether distinct basophil ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2012, 189(9):4371-4378]

Cited: 47 times

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Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation.

David A Hill, Mark C Siracusa, Michael C Abt, Brian S Kim, Dmytro Kobuley, Masato Kubo, Taku Kambayashi, David F Larosa, Ellen D Renner, Jordan S Orange, Frederic D Bushman, David Artis,

Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (T(H)2) cytokine-dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we find that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted ... Read more >>

Nat Med (Nature medicine)
[2012, 18(4):538-546]

Cited: 232 times

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Functional heterogeneity in the basophil cell lineage.

Mark C Siracusa, Elia D Tait Wojno, David Artis,

CD4(+) T-helper type 2 (Th2) cells, characterized by their expression of interleukin (IL)-4, IL-5, IL-9, and IL-13, are required for immunity to helminth parasites and promote the pathological inflammation associated with asthma and allergic diseases. Recent reports from a number of laboratories have indicated that basophils can influence the induction ... Read more >>

Adv Immunol (Advances in immunology)
[2012, 115:141-159]

Cited: 21 times

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TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation.

Mark C Siracusa, Steven A Saenz, David A Hill, Brian S Kim, Mark B Headley, Travis A Doering, E John Wherry, Heidi K Jessup, Lori A Siegel, Taku Kambayashi, Emily C Dudek, Masato Kubo, Antonella Cianferoni, Jonathan M Spergel, Steven F Ziegler, Michael R Comeau, David Artis,

CD4(+) T-helper type 2 (T(H)2) cells, characterized by their expression of interleukin (IL)-4, IL-5, IL-9 and IL-13, are required for immunity to helminth parasites and promote the pathological inflammation associated with asthma and allergic diseases. Polymorphisms in the gene encoding the cytokine thymic stromal lymphopoietin (TSLP) are associated with the ... Read more >>

Nature (Nature)
[2011, 477(7363):229-233]

Cited: 257 times

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