IL-6-JAK2-STAT3 Signaling Pathway and the Pathogenesis of Chronic Tonsillitis

Abstract

Tonsils are among the largest lymphoid tissues within the Waldeyer’s ring. They generate lymphocytes that facilitate immune responses and play essential protective roles in host defense. 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 (>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.