{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:44:15Z","timestamp":1792529055444,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"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 (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to Fc\u03b5RI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L\/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.<\/jats:p>","DOI":"10.3390\/ijms25063248","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T13:08:43Z","timestamp":1710335323000},"page":"3248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-4924","authenticated-orcid":false,"given":"Pio","family":"Conti","sequence":"first","affiliation":[{"name":"Immunology Division, Postgraduate Medical School, University of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaolo","family":"Ronconi","sequence":"additional","affiliation":[{"name":"Clinica dei Pazienti del Territorio, Fondazione Policlinico Gemelli, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-1812","authenticated-orcid":false,"given":"Dorina","family":"Lauritano","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-5675","authenticated-orcid":false,"given":"Filiberto","family":"Mastrangelo","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Foggia, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Caraffa","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8603","authenticated-orcid":false,"given":"Carla E.","family":"Gallenga","sequence":"additional","affiliation":[{"name":"Section of Ophthalmology, Department of Biomedical Sciences and Specialist Surgery, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Frydas","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Aristotle University, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-9928","authenticated-orcid":false,"given":"Spyridon K.","family":"Kritas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Carinci","sequence":"additional","affiliation":[{"name":"Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Gaudelli","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Foggia, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6644-2773","authenticated-orcid":false,"given":"Ciro","family":"Annicchiarico","sequence":"additional","affiliation":[{"name":"Independent Researcher, 70100 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"D\u2019Ovidio","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Medicine and Aging Sciences, G. 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