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When tonsillar crypts are exposed to specific bacterial or viral infections, persistent allergic stimuli, or immune dysregulation, an inflammatory cascade may be triggered, increasing the risk of chronic tonsillitis (CT). CT is a common otolaryngological condition characterized by recurrent episodes of inflammation or a single prolonged episode (&gt;3 months), and it typically presents with repeated acute pharyngalgia, fever, cough, tonsillar swelling and suppuration, itching of the throat, and dryness. The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways, first described by Darnell and Stark in the early 1990s, are highly conserved transmembrane signal transduction mechanisms. They act as central hubs for cytokine-mediated signaling and enable communication between cells and their external environment. Many cytokines exert their biological effects through this pathway. This review elaborates on the activation mechanism of the IL-6-JAK2-STAT3 signaling pathway, summarizes the major drug classes targeting this pathway, highlights the clinical significance in CT, and addresses the current knowledge gaps in the field.<\/jats:p>","DOI":"10.1177\/10799907261442845","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:45:04Z","timestamp":1776426304000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-6-JAK2-STAT3 Signaling Pathway and the Pathogenesis of Chronic Tonsillitis"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3872-7509","authenticated-orcid":false,"given":"Siyu","family":"Li","sequence":"first","affiliation":[{"name":"College of Clinical Medicine, Jining Medical University, Jining, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuguo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Jining First People\u2019s Hospital, Jining, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Jining Medical University, Jining, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojun","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Clinical and Basic Medicine, Shandong First Medical University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4285-117X","authenticated-orcid":false,"given":"Haochen","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Clinical Medicine, Jining Medical University, Jining, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Jining Medical University, Jining, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27227825"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2023.111740"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00058"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.903800"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.129.6.634"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0419-z"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112802"},{"key":"e_1_3_5_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1251914"},{"key":"e_1_3_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12727"},{"key":"e_1_3_5_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204232"},{"issue":"1","key":"e_1_3_5_12_1","first-page":"47","article-title":"[Clinical characteristics and risk factors of recurrent acute infectious epiglottitis in adults]","volume":"37","author":"Gu X","year":"2023","unstructured":"Gu X, , Gao F, , Wang X. 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