{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:00:24Z","timestamp":1790809224862,"version":"4.1.0"},"reference-count":169,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-C-013"],"award-info":[{"award-number":["2022-PUMCH-C-013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, affecting millions annually and leading to substantial mortality, particularly in developing countries. The pathogen\u2019s ability to persist latently and evade host immunity, combined with the emergence of drug-resistant strains, underscores the need for innovative therapeutic strategies. This review highlights the crucial role of interleukin-12 (IL-12) in coordinating immune responses against TB, focusing on its potential as an immunotherapy target. IL-12, a key Th1 cytokine, enhances cellular immunity by promoting Th1 cell differentiation and IFN-\u03b3 production, vital for Mtb clearance. By stimulating cytotoxic T lymphocytes and establishing immune memory, IL-12 supports robust host defense mechanisms. However, the complexity of IL-12 biology, including its roles in pro-inflammatory and regulatory pathways, necessitates a nuanced understanding for effective therapeutic use. Recent studies have shown how IL-12 impacts T cell synapse formation, exosome-mediated bystander activation, and interactions with other cytokines in shaping T cell memory. Genetic defects in the IL-12\/IFN-\u03b3 axis link to susceptibility to mycobacterial diseases, highlighting its importance in TB immunity. The review also addresses challenges like cytokine imbalances seen in TNF-\u03b1\/IFN-\u03b3 synergy, which exacerbate inflammation, and the implications for IL-12-based interventions. Research into modulating IL-12, including its use as an adjuvant and in recombinant vaccines, promises improved TB treatment outcomes and vaccine efficacy. The review concludes by stressing the need for continued investigation into IL-12\u2019s molecular mechanisms towards precision immunotherapies to combat TB and its complications.<\/jats:p>","DOI":"10.3390\/ijms26073106","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:11:40Z","timestamp":1743135100000},"page":"3106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The Role and Potential Application of IL-12 in the Immune Regulation of Tuberculosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0513-1806","authenticated-orcid":false,"given":"Hangxing","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiren","family":"Ruan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanchun","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing 100730, China"},{"name":"Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.ebiom.2015.05.026","article-title":"A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette-Gu\u00e9rin-vaccinated Individuals","volume":"2","author":"Rovetta","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1016\/S2666-5247(22)00359-7","article-title":"WHO\u2019s Global Tuberculosis Report 2022","volume":"4","author":"Bagcchi","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_3","unstructured":"World Health Organization (2022). 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