{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:24:49Z","timestamp":1790958289195,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T00:00:00Z","timestamp":1582329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33\/suppression of tumorigenicity 2 (ST2) axis of mast cell activation\u2014a pathway that is independent of the adaptive immune system\u2014researchers are revisiting other stimuli to induce mast cell activation and\/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn\u2019s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-\u03b21 (TGF-\u03b21) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells\u2019 ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.<\/jats:p>","DOI":"10.3390\/ijms21041498","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T03:33:43Z","timestamp":1582515223000},"page":"1498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Beyond IgE: Alternative Mast Cell Activation Across Different Disease States"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9466-9105","authenticated-orcid":false,"given":"David O.","family":"Lyons","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Northern Colorado, Greeley, CO 80639, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-9278","authenticated-orcid":false,"given":"Nicholas A.","family":"Pullen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Northern Colorado, Greeley, CO 80639, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hsu, C.L., Neilsen, C.V., and Bryce, P.J. (2010). IL-33 is produced by mast cells and regulates IgE-dependent inflammation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011944"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.jaci.2016.09.049","article-title":"IL-33 fine tunes mast cell degranulation and chemokine production at the single-cell level","volume":"140","author":"Joulia","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.immuni.2018.04.025","article-title":"Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells","volume":"48","author":"Gentek","year":"2018","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/imr.12636","article-title":"Is it time for a new classification of mast cells? What do we know about mast cell heterogeneity?","volume":"282","author":"Frossi","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1089\/dna.2013.2005","article-title":"Mast cells: A pivotal role in pulmonary fibrosis","volume":"32","author":"Veerappan","year":"2013","journal-title":"DNA Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.0022-202X.2004.22721.x","article-title":"Human skin mast cells express H2 and H4, but not H3 receptors","volume":"123","author":"Lippert","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_7","first-page":"1058","article-title":"Cloning and Characterization of a Novel Human Histamine Receptor","volume":"296","author":"Morse","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_8","first-page":"45","article-title":"Distribution, properties, and functional characteristics of three classes of histamine receptor","volume":"42","author":"Hill","year":"1990","journal-title":"Pharmacol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tins.2018.09.006","article-title":"Mast Cells in Neuroimmune Interactions","volume":"42","author":"Forsythe","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/imr.12622","article-title":"Mast cell-neural interactions contribute to pain and itch","volume":"282","author":"Gupta","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1365-2567.2007.02705.x","article-title":"Neuropeptides activate human mast cell degranulation and chemokine production","volume":"123","author":"Kulka","year":"2008","journal-title":"Immunology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yoshida, K., Tajima, M., Nagano, T., Obayashi, K., Ito, M., Yamamoto, K., and Matsuoka, I. (2019). Co-Stimulation of Purinergic P2X4 and Prostanoid EP3 Receptors Triggers Synergistic Degranulation in Murine Mast Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205157"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/imr.12633","article-title":"The role of mast cells in autoinflammation","volume":"282","author":"Bonnekoh","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jaci.2016.04.051","article-title":"Roles of Mas-related G protein\u2013coupled receptor X2 on mast cell\u2013mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases","volume":"138","author":"Subramanian","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.bbrc.2006.08.177","article-title":"Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors","volume":"349","author":"Tatemoto","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","first-page":"65","article-title":"Significance of conversation between mast cells and nerves","volume":"1","author":"Bienenstock","year":"2005","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Garcia-Recio, S., and Gasc\u00f3n, P. (2015). Biological and Pharmacological Aspects of the NK1-Receptor. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/495704"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.drudis.2012.05.004","article-title":"Decision-making using fMRI in clinical drug development: Revisiting NK-1 receptor antagonists for pain","volume":"17","author":"Borsook","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1016\/j.bbagen.2017.08.013","article-title":"Mast cell degranulation via MRGPRX2 by isolated human albumin fragments","volume":"1861","author":"Karhu","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature14022","article-title":"Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions","volume":"519","author":"McNeil","year":"2015","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/JLB.2AB1018-405R","article-title":"Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells","volume":"106","author":"Ogasawara","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Belanger, K.A.K., Ameredes, B.T., Boldogh, I., and Aguilera-Aguirre, L. (2016). The Potential Role of 8-Oxoguanine DNA Glycosylase-Driven DNA Base Excision Repair in Exercise-Induced Asthma. Mediators Inflamm., 2016.","DOI":"10.1155\/2016\/3762561"},{"key":"ref_23","first-page":"1345","article-title":"Influence of guanine nucleotides on complex formation between Ras and CDC25 proteins","volume":"13","author":"Lai","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Stunnenberg","year":"2016","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.4049\/jimmunol.138.1.271","article-title":"Interleukin 1 releases histamine from human basophils and mast cells in vitro","volume":"138","author":"Subramanian","year":"1987","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9952","DOI":"10.1016\/S0021-9258(17)36975-2","article-title":"Histamine enhances interleukin (IL)-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells","volume":"269","author":"Vannier","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1002\/ibd.21478","article-title":"NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis","volume":"17","author":"Hirota","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_29","first-page":"339","article-title":"Environmental risk factors for inflammatory bowel disease","volume":"6","author":"Molodecky","year":"2010","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(07)60750-8","article-title":"Series Gastroenterology 1 Infl ammatory bowel disease: Cause and immunobiology","volume":"369","author":"Baumgart","year":"2007","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1136\/gut.2010.228908","article-title":"Crohn\u2019s disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2","volume":"60","author":"Plantinga","year":"2011","journal-title":"Gut"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1136\/gut.40.2.234","article-title":"Altered expression of mucins throughout the colon in ulcerative colitis","volume":"40","author":"Smithson","year":"1997","journal-title":"Gut"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1084\/jem.20110547","article-title":"Host innate recognition of an intestinal bacterial pathogen induces TRIF-dependent protective immunity","volume":"208","author":"Sotolongo","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s11894-010-0132-1","article-title":"Mast Cells","volume":"12","author":"Stiltz","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/imr.12629","article-title":"Non-IgE mediated mast cell activation","volume":"282","author":"Redegeld","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.1128\/IAI.68.12.7010-7017.2000","article-title":"Differential Alteration in Intestinal Epithelial Cell Expression of Toll-Like Receptor 3 (TLR3) and TLR4 in Inflammatory Bowel Disease","volume":"68","author":"Cario","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1093\/hmg\/ddi135","article-title":"Association between a complex insertion\/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease","volume":"14","author":"McGovern","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","first-page":"908","article-title":"Rectal substance P concentrations are increased in ulcerative colitis but not in Crohn\u2019s disease","volume":"88","author":"Bernstein","year":"1993","journal-title":"Am. J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1136\/gut.52.1.84","article-title":"Changes in chemical coding of myenteric neurones in ulcerative colitis","volume":"52","author":"Neunlist","year":"2003","journal-title":"Gut"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chompunud, C., Ayudhya, N., Roy, S., Alkanfari, I., Ganguly, A., and Ali, H. (2019). Identification of Gain and Loss of Function Missense Variants in MRGPRX2\u2019 s Transmembrane and Intracellular Domains for Mast Cell Activation by Substance P. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215247"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.2353\/ajpath.2010.100378","article-title":"Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts","volume":"177","author":"Sponheim","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3748\/wjg.14.165","article-title":"Hygiene hypothesis in inflammatory bowel disease: A critical review of the literature","volume":"14","author":"Koloski","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.0269-2813.2004.01803.x","article-title":"Review article: Helminths as therapeutic agents for inflammatory bowel disease","volume":"19","author":"Hunter","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/mi.2017.121","article-title":"Histamine drives severity of innate inflammation via histamine 4 receptor in murine experimental colitis","volume":"11","author":"Wechsler","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E4002","DOI":"10.1073\/pnas.1524845114","article-title":"SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors","volume":"114","author":"Taracanova","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.4049\/jimmunol.1600066","article-title":"IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10\u2013Deficient Mice","volume":"196","author":"Polukort","year":"2016","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"813","DOI":"10.4049\/jimmunol.1801156","article-title":"Cutaneous Exposure to Clinically Relevant Lone Star Ticks Promotes IgE Production and Hypersensitivity through CD4 + T Cell\u2013 and MyD88-Dependent Pathways in Mice","volume":"203","author":"Chandrasekhar","year":"2019","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.jaci.2016.03.056","article-title":"IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells","volume":"138","author":"Galand","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.immuni.2015.08.020","article-title":"Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy","volume":"43","author":"Chen","year":"2015","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-22716-9","article-title":"IL-33\/ST2 signalling and crosstalk with Fc\u03f5RI and TLR4 is targeted by the parasitic worm product, ES-62","volume":"8","author":"Ball","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kropp, L., Jackson-Thompson, B., Thomas, L.M., McDaniel, D., and Mitre, E. (2019). Chronic infection with a tissue invasive helminth attenuates sublethal anaphylaxis and reduces granularity and number of mast cells. Clin. Exp. Allergy.","DOI":"10.1111\/cea.13549"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13073","DOI":"10.1073\/pnas.1311861110","article-title":"Dietary gluten triggers concomitant activation of CD4+ and CD8+ \u03b1\u03b2 T cells and \u03b3\u03bb T cells in celiac disease","volume":"110","author":"Han","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.jaci.2016.08.011","article-title":"Mast cells are associated with the onset and progression of celiac disease","volume":"139","author":"Frossi","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1136\/gut.24.3.222","article-title":"Human intestinal mucosal mast cells: Expanded population in untreated coeliac disease","volume":"24","author":"Strobel","year":"1983","journal-title":"Gut"},{"key":"ref_55","unstructured":"Himmelweit, F. (1960). The Collected Papers of Paul Ehrlich, Elsevier."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"(2019). Varricchi; de Paulis; Marone; Galli Future Needs in Mast Cell Biology. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184397"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Okano, M., Oshi, M., Butash, A.L., Katsuta, E., Tachibana, K., Saito, K., Okayama, H., Peng, X., Yan, L., and Kono, K. (2019). Triple-Negative Breast Cancer with High Levels of Annexin A1 Expression Is Associated with Mast Cell Infiltration, Inflammation, and Angiogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174197"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"201716804","DOI":"10.1073\/pnas.1716804115","article-title":"Mast cells promote small bowel cancer in a tumor stage-specific and cytokine-dependent manner","volume":"115","author":"Saadalla","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1158\/0008-5472.CAN-14-3767","article-title":"Mast cells infiltrating inflamed or transformed gut alternatively sustain mucosal healing or tumor growth","volume":"75","author":"Rigoni","year":"2015","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1189\/jlb.0913510","article-title":"Myeloid-derived suppressor cells enhance IgE-mediated mast cell responses","volume":"95","author":"Morales","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0016-5085(98)70381-6","article-title":"Inflammatory bowel disease: Etiology and pathogenesis","volume":"115","author":"Fiocchi","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Itzkowitz, S.H., and Yio, X. (2004). Inflammation and cancer - IV. Colorectal cancer in inflammatory bowel disease: The role of inflammation. Am. J. Physiol. Gastrointest. Liver Physiol., 287.","DOI":"10.1152\/ajpgi.00079.2004"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1084\/jem.20100050","article-title":"The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer","volume":"207","author":"Allen","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.4049\/jimmunol.1002046","article-title":"IL-18 Production Downstream of the Nlrp3 Inflammasome Confers Protection against Colorectal Tumor Formation","volume":"185","author":"Zaki","year":"2010","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12943-018-0900-3","article-title":"Role of the NLRP3 inflammasome in cancer","volume":"17","author":"Moossavi","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/bjd.12631","article-title":"Bimodal immune activation in psoriasis","volume":"170","author":"Christophers","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.it.2013.04.001","article-title":"From genetics of inflammatory bowel disease towards mechanistic insights","volume":"34","author":"Graham","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1523\/JNEUROSCI.20-01-00401.2000","article-title":"Mast cells migrate from blood to brain","volume":"20","author":"Silverman","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1097\/bor.0000174210.78449.6b","article-title":"Familial autoinflammatory diseases: Genetics, pathogenesis and treatment","volume":"17","author":"Stojanov","year":"2005","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.4049\/jimmunol.174.10.5987","article-title":"TGF-beta 1 inhibits mast cell Fc epsilon RI expression","volume":"174","author":"Gomez","year":"2005","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1136\/gut.2004.054650","article-title":"Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor \u03b21","volume":"54","author":"Gebhardt","year":"2005","journal-title":"Gut"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.2353\/ajpath.2009.080723","article-title":"Homeostatic role of transforming growth factor-\u03b2 in the oral cavity and esophagus of mice and its expression by mast cells in these tissues","volume":"174","author":"Vitsky","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/jlb.67.3.350","article-title":"Human mast cell migration in response to members of the transforming growth factor-beta family","volume":"67","author":"Olsson","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4049\/jimmunol.156.1.73","article-title":"TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice","volume":"156","author":"Maeda","year":"1996","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lyons, D.O., Plewes, M.R., and Pullen, N.A. (2018). Soluble transforming growth factor beta-1 enhances murine mast cell release of Interleukin 6 in IgE-independent and Interleukin 13 in IgE-dependent settings in vitro. PLoS ONE, 1\u201317.","DOI":"10.1371\/journal.pone.0207704"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"594","DOI":"10.4049\/jimmunol.1102389","article-title":"Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-\u03b2","volume":"188","author":"Ganeshan","year":"2012","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jaci.2015.01.033","article-title":"Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis","volume":"136","author":"Mashiko","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"490","DOI":"10.4049\/jimmunol.1100123","article-title":"Mast Cells and Neutrophils Release IL-17 through Extracellular Trap Formation in Psoriasis","volume":"187","author":"Lin","year":"2011","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/eji.201040994","article-title":"Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function","volume":"41","author":"Dudeck","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.4049\/jimmunol.1203362","article-title":"TGF-\u03b21 Limits the Onset of Innate Lung Inflammation by Promoting Mast Cell-Derived IL-6","volume":"190","author":"Ganeshan","year":"2013","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kasakura, K., Nagata, K., Miura, R., Nakaya, H., Okada, H., Arai, T., Arai, T., Kawakami, Y., Kawakami, T., and Yashiro, T. (2020). Cooperative Regulation of the Mucosal Mast Cell\u2212Specific Protease Genes Mcpt1 and Mcpt2 by GATA and Smad Transcription Factors. J. Immunol.","DOI":"10.4049\/jimmunol.1900094"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20500","DOI":"10.1073\/pnas.1908816116","article-title":"Mast cells are critical for controlling the bacterial burden and the healing of infected wounds","volume":"116","author":"Zimmermann","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.4049\/jimmunol.1900637","article-title":"IL-10 Has Differential Effects on the Innate and Adaptive Immune Systems of Septic Patients","volume":"203","author":"Mazer","year":"2019","journal-title":"J. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep14488","article-title":"Chronic TLR Stimulation Controls NLRP3 Inflammasome Activation through IL-10 Mediated Regulation of NLRP3 Expression and Caspase-8 Activation","volume":"5","author":"Gurung","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13075-014-0419-y","article-title":"Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction","volume":"16","author":"Greenhill","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1001\/archsurg.1989.01410120082016","article-title":"Endotoxin Tolerance Is Associated with Reduced Secretion of Tumor Necrosis Factor","volume":"124","year":"1989","journal-title":"Arch. Surg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.4049\/jimmunol.1800997","article-title":"TLR4 Receptor Induces 2-AG\u2013Dependent Tolerance to Lipopolysaccharide and Trafficking of CB2 Receptor in Mast Cells","volume":"202","author":"Vibhushan","year":"2019","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1084\/jem.181.5.1887","article-title":"Mechanism of endotoxin desensitization: Involvement of interhukin 10 and transforming growth factor \u03b2","volume":"181","author":"Randow","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5537","DOI":"10.4049\/jimmunol.160.11.5537","article-title":"Reversible expression of tryptases and chymases in the jejunal mast cells of mice infected with Trichinella spiralis","volume":"160","author":"Friend","year":"1998","journal-title":"J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1083\/jcb.135.1.279","article-title":"Mast cells that reside at different locations in the jejunum of mice infected with Trichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype","volume":"135","author":"Friend","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Varricchi, G., Pecoraro, A., Loffredo, S., Poto, R., Rivellese, F., Genovese, A., Marone, G., and Spadaro, G. (2019). Heterogeneity of human mast cells with respect to MRGPRX2 receptor expression and function. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00299"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.4049\/jimmunol.1201959","article-title":"Inflammasome-Independent NLRP3 Augments TGF-\u03b2 Signaling in Kidney Epithelium","volume":"190","author":"Wang","year":"2013","journal-title":"J. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00125-011-2391-2","article-title":"Pathogenic role of mast cells in the development of diabetic nephropathy: A study of patients at different stages of the disease","volume":"55","author":"Zheng","year":"2012","journal-title":"Diabetologia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1159\/000057367","article-title":"Link between Angiotensin II and TGF-\u03b2 in the Kidney","volume":"24","author":"Wolf","year":"1998","journal-title":"Miner. Electrolyte Metab."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Wang, Z., Guhl, S., Franke, K., Artuc, M., Zuberbier, T., and Babina, M. (2019). IL-33 and MRGPRX2-Triggered Activation of Human Skin Mast Cells\u2014Elimination of Receptor Expression on Chronic Exposure, but Reinforced Degranulation on Acute Priming. Cells, 8.","DOI":"10.3390\/cells8040341"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/ijc.28481","article-title":"Interleukin-33\/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells","volume":"134","author":"Jovanovic","year":"2014","journal-title":"Int. J. Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:59:58Z","timestamp":1760173198000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,22]]},"references-count":97,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21041498"],"URL":"https:\/\/doi.org\/10.3390\/ijms21041498","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,22]]}}}