Calviño-Suárez, CristinaDurán Rubí, MariñaBrea Floriani, José ManuelMoreira Álvarez, DavidArdao Palacios, InésBrocos Mosquera, IriaFerreiro Iglesias, RocíoPorto Silva, SolNieto-García, LauraVarela Liste, María JoséLoza García, María IsabelMartínez Rodríguez, Antón LeandroBarreiro de Acosta, Manuel2025-07-222025-07-222025-07-21Calviño-Suarez C, Duran-Rubi M, Brea J, Moreira D, Ardao I, Brocos-Mosquera I, Ferreiro-Iglesias R, Porto-Silva S, Nieto-Garcia L, Varela MJ, Loza MI, Martinez AL and Barreiro-de Acosta M (2025) Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response. Front. Immunol. 16:1609740.https://hdl.handle.net/10347/42564Introduction. Ulcerative colitis (UC) is characterized by aberrant immune responses involving multiple inflammatory pathways, including JAK/STAT signaling. However, the specific roles and interactions of individual components within this pathway remain unclear. Methods. We conducted a prospective, observational, single-center study enrolling 61 adult UC patients undergoing routine colonoscopy with endoscopic activity (Mayo Endoscopic Score > 0). Paired biopsies from inflamed and non-inflamed colonic mucosa were collected. Phosphorylation levels of JAK1, JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 were quantified by Western blot. Results. Inflamed tissue showed significantly increased phosphorylation of JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 compared to non-inflamed mucosa (p < 0.05), while JAK1 levels did not differ significantly. Correlation analysis revealed coordinated activation among JAK2, JAK3, TYK2, and STAT3, suggesting interdependent roles. Notably, male patients exhibited significantly higher activation of JAK2 and STAT3 than female patients (p < 0.05). Discussion. These findings highlight a heterogeneous but important involvement of the JAK/STAT pathway in UC pathophysiology. The observed sex-specific differences and coordinated activation patterns suggest the value of personalized therapeutic approaches targeting specific components of this pathway.eng© 2025 Calviño-Suarez, Duran-Rubi, Brea, Moreira, Ardao, Brocos-Mosquera, Ferreiro-Iglesias, Porto-Silva, Nieto-Garcia, Varela, Loza, Martinez and Barreiro-de Acosta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Ulcerative colitisJAK/STAT pathwayPhosphorylationSex-specific differencesInflammatory signalingPersonalized therapyjournal article10.3389/fimmu.2025.1609740open access