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exact known cause. Intestinal innate immunity is enacted by neutrophils, monocytes, macrophages, and dendritic cells (DCs), and innate lymphoid cells and NK cells, characterized by their capacity to produce a rapid and nonspecific reaction as a first-line response. Innate immune cells (IIC) defend against pathogens and excessive entry of intestinal microorganisms, while preserving immune tolerance to resident intestinal microbiota. Changes to this equilibrium are linked to intestinal inflammation in the gut and IBD. IICs mediate host defense responses, inflammation, and tissue healing by producing cytokines and chemokines, activating the complement cascade and phagocytosis, or presenting antigens to activate the adaptive immune response. IICs exert important functions that promote or ameliorate the cellular and molecular mechanisms that underlie and sustain IBD. A comprehensive understanding of the mechanisms underlying these clinical manifestations will be important for developing therapies targeting the innate immune system in IBD patients. This review examines the complex roles of and interactions among IICs, and their interactions with other immune and non-immune cells in homeostasis and pathological conditions.<\/jats:p>","DOI":"10.3390\/ijms24021526","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T01:30:26Z","timestamp":1673573426000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":591,"title":["Pathophysiology of Inflammatory Bowel Disease: Innate Immune System"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-4737","authenticated-orcid":false,"given":"Angela","family":"Saez","sequence":"first","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria (UFV), 28223 Pozuelo de Alarc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Herrero-Fernandez","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6665-7732","authenticated-orcid":false,"given":"Raquel","family":"Gomez-Bris","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"S\u00e1nchez-Martinez","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1177-869X","authenticated-orcid":false,"given":"Jose M.","family":"Gonzalez-Granado","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrgastro.2017.136","article-title":"Environmental triggers in IBD: A review of progress and evidence","volume":"15","author":"Ananthakrishnan","year":"2018","journal-title":"Nat. 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