{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:03:14Z","timestamp":1772553794441,"version":"3.50.1"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mast cells (MCs) are multifunctional innate immune cells that regulate inflammation, tissue repair, and immune responses, and they are increasingly recognized as contributors to chronic liver disease. In parallel, the aryl hydrocarbon receptor (AhR) has emerged as a key environmental sensor activated by gut-derived tryptophan metabolites such as kynurenine and microbial indoles. The current literature separately describes the role of AhR in MC signaling, as well as the contributions of MCs to liver pathology and the disrupted gut\u2013liver axis, which drives immune dysfunction in chronic liver disease. However, these aspects have been rarely considered together. This review aims to bridge these fragmented areas, providing an integrated framework where AhR-driven MC responses are examined within the gut\u2013liver axis along with their impacts on liver inflammation and fibrosis. We discuss how this microbial\u2013immune dialogue shapes autoimmune and cholestatic liver diseases, including autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cholangitis. Finally, we highlight translational perspectives, from microbiota modulation to AhR-targeting approaches, as potential strategies to control MC-driven hepatic inflammation. By integrating these currently separate concepts, this review offers a novel perspective on the role of MCs as important mediators at the interface of gut-derived signals and liver pathology via AhR signaling, while highlighting innovative therapeutic avenues through the modulation of the microbiota, targeting of AhR, and regulation of MC responses.<\/jats:p>","DOI":"10.3390\/cells15050449","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:48:56Z","timestamp":1772542136000},"page":"449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mast Cells at the Crossroad of Gut-Derived Signals Through Aryl Hydrocarbon Receptor Activation: A Microbial\u2013Immune Dialogue in Liver Inflammation with Therapeutic Perspectives"],"prefix":"10.3390","volume":"15","author":[{"given":"Francesco","family":"Vasuri","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"},{"name":"Pathology Unit, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9855-2396","authenticated-orcid":false,"given":"Barbara","family":"Frossi","sequence":"additional","affiliation":[{"name":"Immunology Section, Department of Medicine, University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Saragoni","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"},{"name":"Pathology Unit, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-0459","authenticated-orcid":false,"given":"Giorgia","family":"Gri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152458","DOI":"10.1016\/j.tox.2020.152458","article-title":"Kynurenine produced by indoleamine 2,3-dioxygenase 2 exacerbates acute liver injury by carbon tetrachloride in mice","volume":"438","author":"Hoshi","year":"2020","journal-title":"Toxicology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107845","DOI":"10.1016\/j.pharmthera.2021.107845","article-title":"Kynurenine emerges from the shadows\u2014Current knowledge on its fate and function","volume":"225","author":"Walczak","year":"2021","journal-title":"Pharmacol. 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