{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:01:37Z","timestamp":1790262097833,"version":"4.1.0"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017445","name":"Science Fund for Distinguished Young Scholars of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) is a fatal complication, in which the progression of pulmonary fibrosis has been closely linked to immune microenvironment imbalance and oxidative stress. Regulatory T cells (Tregs), as a central component of immune tolerance, play a crucial role in suppressing excessive inflammation. Current evidence suggests that oxidative stress may contribute to Treg dysregulation through several interrelated mechanisms, including redox-sensitive regulation of Foxp3 expression and stability, disruption of IL-2 signaling, and remodeling of the inflammatory microenvironment. However, the majority of the mechanistic evidence is derived from experimental models or related autoimmune and inflammatory conditions, with limited direct validation in patients with SARD-ILD. These proposed interactions may contribute to a self-reinforcing cycle of oxidative stress and Treg dysregulation, potentially promoting effector T-cell activation, fibroblast proliferation, and imbalanced inflammation and repair, thereby contributing to pulmonary fibrotic remodeling. This review integrates current evidence on the potential links among oxidative stress, Treg dysregulation, and pulmonary fibrosis in SARD-ILD, and proposes an emerging mechanistic framework to guide further investigation into their possible interactions and therapeutic implications.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1882853","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:02:16Z","timestamp":1790258536000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Treg dysregulation in the oxidative lung milieu: an emerging mechanistic link in interstitial lung disease associated with systemic autoimmune rheumatic diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital)","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital)","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital)","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital)","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2416840","DOI":"10.1016\/j.pulmoe.2023.11.007","article-title":"Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society","volume":"31","author":"Morais","year":"2025","journal-title":"Pulmonology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"250046","DOI":"10.1183\/16000617.0046-2025","article-title":"Treating connective tissue disease-associated interstitial lung disease - think outside the box: A perspective","volume":"34","author":"Khor","year":"2025","journal-title":"Eur Respir Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41584-021-00721-z","article-title":"Acute exacerbation of interstitial lung disease associated with rheumatic disease","volume":"18","author":"Luppi","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61079-4","article-title":"Interstitial lung disease in connective tissue disorders","volume":"380","author":"Fischer","year":"2012","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/art.40769","article-title":"Proceedings of the American College of Rheumatology\/Association of Physicians of Great Britain and Ireland connective tissue disease-associated interstitial lung disease summit: A multidisciplinary approach to address challenges and opportunities","volume":"71","author":"Fischer","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/art.43326","article-title":"Case-based immunology: B cells and systemic sclerosis interstitial lung disease","volume":"78","author":"Goldman","year":"2026","journal-title":"Arthritis Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202110-2414OC","article-title":"Comprehensive analysis of fibroblast activation protein expression in interstitial lung diseases","volume":"207","author":"Yang","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01052-2","article-title":"Interstitial lung diseases","volume":"400","author":"Wijsenbeek","year":"2022","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e180252","DOI":"10.1172\/JCI180252","article-title":"Activated Sting in the thymic epithelium alters T cell development and selection leading to autoimmunity","volume":"135","author":"Deng","year":"2025","journal-title":"J Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108562","article-title":"Emerging role of immune cells as drivers of pulmonary fibrosis","volume":"252","author":"Mutsaers","year":"2023","journal-title":"Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.015","article-title":"Immune mechanisms in fibrotic interstitial lung disease","volume":"187","author":"Kamiya","year":"2024","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e20221676","DOI":"10.1084\/jem.20221676","article-title":"Regulatory T cells suppress Cd4+ effector T cell activation by controlling protein synthesis","volume":"220","author":"So","year":"2023","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c190017","article-title":"Oxidative stress in pulmonary fibrosis","volume":"10","author":"Otoupalova","year":"2020","journal-title":"Compr Physiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.11.021","article-title":"Oxidative stress and pulmonary fibrosis","volume":"1832","author":"Cheresh","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e182480","DOI":"10.1172\/JCI182480","article-title":"Acetyl-Coa carboxylase 1 inhibition increases Treg metabolism and graft-versus-host disease treatment efficacy via mitochondrial fusion","volume":"135","author":"McDonald-Hyman","year":"2025","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103590","article-title":"Ros-dependent Socs3 upregulation disrupts regulatory T cell stability during autoimmune disease development","volume":"82","author":"Satooka","year":"2025","journal-title":"Redox Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.06.007","article-title":"Breaking tolerance: An update of Treg dysfunction in autoimmunity","volume":"46","author":"Cheru","year":"2025","journal-title":"Trends Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103059","article-title":"A novel role for the Ros-Atm-Chk2 axis mediated metabolic and cell cycle reprogramming in the M1 macrophage polarization","volume":"70","author":"Li","year":"2024","journal-title":"Redox Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3466","article-title":"Immunometabolism of regulatory T cells","volume":"17","author":"Newton","year":"2016","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00575-z","article-title":"Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics","volume":"4","author":"Liu","year":"2022","journal-title":"Nat Metab"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e170505","DOI":"10.1172\/JCI170505","article-title":"Differential roles of regulatory T cells in acute respiratory infections","volume":"133","author":"Jovisic","year":"2023","journal-title":"J Clin Invest"},{"key":"B22","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/s41467-023-36594-x","article-title":"Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming","volume":"14","author":"Aso","year":"2023","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01036-7","article-title":"Intricacies of Tgf-beta signaling in Treg and Th17 cell biology","volume":"20","author":"Wang","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e173593","DOI":"10.1172\/JCI173593","article-title":"Dysregulated Treg repair responses lead to chronic rejection after heart transplantation","volume":"134","author":"Warunek","year":"2024","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adk5041","article-title":"An aging bone marrow exacerbates lung fibrosis by fueling profibrotic macrophage persistence","volume":"10","author":"Farhat","year":"2025","journal-title":"Sci Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01048","article-title":"Foxp3(+) T regulatory cells: Still many unanswered questions-a perspective after 20 years of study","volume":"9","author":"Shevach","year":"2018","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202502-0419OC","article-title":"Active antigen-specific adaptive immune responses are shared among patients with progressive fibrotic interstitial lung disease","volume":"211","author":"Velez","year":"2025","journal-title":"Am J Respir Crit Care Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.75","article-title":"The regulation of immune tolerance by Foxp3","volume":"17","author":"Lu","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00893-7","article-title":"The role of transcription factors in shaping regulatory T cell identity","volume":"23","author":"Trujillo-Ochoa","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206692","article-title":"Batf is required for Treg homeostasis and stability to prevent autoimmune pathology","volume":"10","author":"Khatun","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.04.005","article-title":"Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells","volume":"54","author":"Kawakami","year":"2021","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.031","article-title":"T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of Il-12 receptor beta2","volume":"37","author":"Koch","year":"2012","journal-title":"Immunity"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.02.012","article-title":"Treg cells expressing the coinhibitory molecule Tigit selectively inhibit proinflammatory Th1 and Th17 cell responses","volume":"40","author":"Joller","year":"2014","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202012-4306OC","article-title":"Obesity-related Il-18 impairs T-regulatory cell function and promotes lung ischemia-reperfusion injury","volume":"204","author":"Akimova","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.07.010","article-title":"Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity","volume":"57","author":"Ichiyama","year":"2024","journal-title":"Immunity"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/art.42111","article-title":"Driving role of interleukin-2-related regulatory Cd4+ T cell deficiency in the development of lung fibrosis and vascular remodeling in a mouse model of systemic sclerosis","volume":"74","author":"Frantz","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.7150\/thno.82069","article-title":"Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension","volume":"13","author":"Guo","year":"2023","journal-title":"Theranostics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7150\/thno.74809","article-title":"Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae","volume":"12","author":"Chen","year":"2022","journal-title":"Theranostics"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812-1936OC","article-title":"Global impairment of Cd4+Cd25+Foxp3+ regulatory T cells in idiopathic pulmonary fibrosis","volume":"179","author":"Kotsianidis","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201206-1109OC","article-title":"Semaphorin 7a+ regulatory T cells are associated with progressive idiopathic pulmonary fibrosis and are implicated in transforming growth factor-beta1-induced pulmonary fibrosis","volume":"187","author":"Reilkoff","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e138519","DOI":"10.1172\/JCI138519","article-title":"Oleic acid restores suppressive defects in tissue-resident Foxp3 Tregs from patients with multiple sclerosis","volume":"131","author":"Pompura","year":"2021","journal-title":"J Clin Invest"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.08.009","article-title":"A regulator of amino acid sensing links lipid peroxidation and lipid droplet-dependent antioxidant response","volume":"85","author":"Li","year":"2025","journal-title":"Mol Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101947","article-title":"Nox4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases","volume":"41","author":"Park","year":"2021","journal-title":"Redox Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102709","article-title":"Mitochondrial fusion induced by transforming growth factor-beta1 serves as a switch that governs the metabolic reprogramming during differentiation of regulatory T cells","volume":"62","author":"Fang","year":"2023","journal-title":"Redox Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nri3423","article-title":"Beyond oxidative stress: An immunologist's guide to reactive oxygen species","volume":"13","author":"Nathan","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.03.034","article-title":"Ros function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152925","article-title":"Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis","volume":"11","author":"Mateen","year":"2016","journal-title":"PloS One"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.04.006","article-title":"Metabolism as a target for modulation in autoimmune diseases","volume":"39","author":"Huang","year":"2018","journal-title":"Trends Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adr7057","article-title":"Inducible protein degradation reveals inflammation-dependent function of the T(Reg) cell lineage-defining transcription factor Foxp3","volume":"10","author":"Jager","year":"2025","journal-title":"Sci Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02166-y","article-title":"Succinate drives gut inflammation by promoting Foxp3 degradation through a molecular switch","volume":"26","author":"Wang","year":"2025","journal-title":"Nat Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00969-9","article-title":"Usp1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing Taz","volume":"20","author":"Zhu","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00790-w","article-title":"Activation of Ampkalpha1 is essential for regulatory T cell function and autoimmune liver disease prevention","volume":"18","author":"Zhu","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170523","article-title":"Pten drives Th17 cell differentiation by preventing Il-2 production","volume":"214","author":"Kim","year":"2017","journal-title":"J Exp Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3076","article-title":"Treg cells require the phosphatase Pten to restrain Th1 and Tfh cell responses","volume":"16","author":"Shrestha","year":"2015","journal-title":"Nat Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3077","article-title":"Control of Pi(3) kinase in Treg cells maintains homeostasis and lineage stability","volume":"16","author":"Huynh","year":"2015","journal-title":"Nat Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.703972","article-title":"Targeting mitochondrial-derived reactive oxygen species in T cell-mediated autoimmune diseases","volume":"12","author":"Chavez","year":"2021","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.020","article-title":"Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling","volume":"38","author":"Sena","year":"2013","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.030","article-title":"Function of a Foxp3 cis-element in protecting regulatory T cell identity","volume":"158","author":"Li","year":"2014","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1278560","article-title":"Metabolic regulation of Forkhead box P3 alternative splicing isoforms and their impact on health and disease","volume":"14","author":"Luo","year":"2023","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89160","article-title":"Foxp3 drives oxidative phosphorylation and protection from lipotoxicity","volume":"2","author":"Howie","year":"2017","journal-title":"JCI Insight"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.03.020","article-title":"A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance","volume":"54","author":"Dikiy","year":"2021","journal-title":"Immunity"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e20200795","DOI":"10.1084\/jem.20200795","article-title":"Lymph node fibroblastic reticular cells regulate differentiation and function of Cd4 T cells via Cd25","volume":"219","author":"Kim","year":"2022","journal-title":"J Exp Med"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e180080","DOI":"10.1172\/JCI180080","article-title":"Spatial and functional targeting of intratumoral Tregs reverses Cd8+ T cell exhaustion and promotes cancer immunotherapy","volume":"134","author":"Zhou","year":"2024","journal-title":"J Clin Invest"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103240","article-title":"Peroxynitrite reduces Treg cell expansion and function by mediating Il-2r nitration and aggravates multiple sclerosis pathogenesis","volume":"75","author":"Wu","year":"2024","journal-title":"Redox Biol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e012182","DOI":"10.1136\/jitc-2025-012182","article-title":"Macrophage Nlrp3 activation and Il-1beta release drive osimertinib-induced antitumor immunity","volume":"13","author":"Yu","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221985","article-title":"Tfh cells with Nlrp3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity","volume":"81","author":"Zhao","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202500849","article-title":"Oxytocin-mediate modulation of splenic immunosuppression in chronic social stress through neuroendocrine pathways","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B68","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1186\/s12951-024-02855-0","article-title":"Superior antitumor immune response achieved with proton over photon immunoradiotherapy is amplified by the nanoradioenhancer Nbtxr3","volume":"22","author":"Hu","year":"2024","journal-title":"J Nanobiotechnol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c12498","article-title":"Multifunctional redox-responsive nanoplatform with dual activation of macrophages and T cells for antitumor immunotherapy","volume":"17","author":"Zhang","year":"2023","journal-title":"ACS Nano"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.09.016","article-title":"Burning the candle at both ends: Ros-mediated telomere damage drives T cell dysfunction","volume":"58","author":"Wesolowski","year":"2025","journal-title":"Immunity"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-25-4716","article-title":"Between Ros and a hard place: Telomere damage as a driver of T-cell exhaustion","volume":"86","author":"Mitra","year":"2026","journal-title":"Cancer Res"},{"key":"B72","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1053\/j.gastro.2022.09.006","article-title":"Th17 cell-derived amphiregulin promotes colitis-associated intestinal fibrosis through activation of Mtor and Mek in intestinal myofibroblasts","volume":"164","author":"Zhao","year":"2023","journal-title":"Gastroenterology"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08542-2","article-title":"Runx2 promotes fibrosis via an alveolar-to-pathological fibroblast transition","volume":"640","author":"Fang","year":"2025","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c08033","article-title":"Combining microfluidic assessment with encoded hydrogel microparticle-based immunoassay for anti-interleukin drug repurposing of pulmonary fibrosis therapy","volume":"19","author":"Kim","year":"2025","journal-title":"ACS Nano"},{"key":"B75","doi-asserted-by":"publisher","first-page":"4502","DOI":"10.1038\/s41467-022-32195-2","article-title":"In mouse chronic pancreatitis Cd25(+)Foxp3(+) regulatory T cells control pancreatic fibrosis by suppression of the type 2 immune response","volume":"13","author":"Glaubitz","year":"2022","journal-title":"Nat Commun"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/acr.25348","article-title":"2023 American College of Rheumatology (Acr)\/American College of Chest Physicians (Chest) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases","volume":"76","author":"Johnson","year":"2024","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.cmet.2023.01.009","article-title":"Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs","volume":"35","author":"Corte-Real","year":"2023","journal-title":"Cell Metab"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113354","article-title":"Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis","volume":"366","author":"Raghu","year":"2012","journal-title":"N Engl J Med"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401739","article-title":"Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis","volume":"370","author":"Martinez","year":"2014","journal-title":"N Engl J Med"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00702-2","article-title":"Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid beta aggregates in vivo in a mouse model of Alzheimer's disease","volume":"19","author":"Calvo-Rodriguez","year":"2024","journal-title":"Mol Neurodegener"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2016.1199957","article-title":"Restoring regulation - Il-2 therapy in systemic lupus erythematosus","volume":"12","author":"Humrich","year":"2016","journal-title":"Expert Rev Clin Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207776","article-title":"Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus","volume":"75","author":"von Spee-Mayer","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222501","article-title":"Low-dose interleukin-2 therapy in active systemic lupus erythematosus (Lupil-2): A multicentre, double-blind, randomised and placebo-controlled phase II trial","volume":"81","author":"Humrich","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.07.016","article-title":"Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics","volume":"57","author":"Raeber","year":"2024","journal-title":"Immunity"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108188","article-title":"Interleukin-2 and regulatory T cells in graft-versus-host disease","volume":"365","author":"Koreth","year":"2011","journal-title":"N Engl J Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105143","article-title":"Regulatory T-cell responses to low-dose interleukin-2 in Hcv-induced vasculitis","volume":"365","author":"Saadoun","year":"2011","journal-title":"N Engl J Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S2213-8587(13)70113-X","article-title":"Low-dose interleukin 2 in patients with type 1 diabetes: A phase 1\/2 randomised, double-blind, placebo-controlled trial","volume":"1","author":"Hartemann","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jaut.2015.01.001","article-title":"Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1d patients","volume":"58","author":"Rosenzwajg","year":"2015","journal-title":"J Autoimmun"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900980","article-title":"Regulatory T cells limit pneumococcus-induced exacerbation of lung fibrosis in mice","volume":"204","author":"Moye","year":"2020","journal-title":"J Immunol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The Jak\/Stat signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.3390\/pharmaceutics14051001","article-title":"A comprehensive overview of globally approved Jak inhibitors","volume":"14","author":"Shawky","year":"2022","journal-title":"Pharmaceutics"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102303","article-title":"Tyk2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation","volume":"6","author":"Tuomela","year":"2025","journal-title":"Cell Rep Med"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024026446","article-title":"Donor regulatory T-cell therapy to prevent graft-versus-host disease","volume":"145","author":"Meyer","year":"2025","journal-title":"Blood"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011625","article-title":"Single-center randomized trial of T-Reg graft alone vs T-Reg graft plus tacrolimus for the prevention of acute Gvhd","volume":"8","author":"Bader","year":"2024","journal-title":"Blood Adv"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adm8859","article-title":"Harnessing regulatory T cells to establish immune tolerance","volume":"16","author":"Ho","year":"2024","journal-title":"Sci Transl Med"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.04.005","article-title":"Engineered Treg cells as putative therapeutics against inflammatory diseases and beyond","volume":"44","author":"Bittner","year":"2023","journal-title":"Trends Immunol"},{"key":"B97","doi-asserted-by":"publisher","first-page":"1901949","DOI":"10.1183\/13993003.01949-2019","article-title":"Nadph oxidase Duox1 sustains Tgf-beta1 signalling and promotes lung fibrosis","volume":"57","author":"Louzada","year":"2021","journal-title":"Eur Respir J"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220493","article-title":"Integrative analysis of lung molecular signatures reveals key drivers of systemic sclerosis-associated interstitial lung disease","volume":"81","author":"Jung","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1002\/art.42286","article-title":"Epigenetic regulation of profibrotic macrophages in systemic sclerosis-associated interstitial lung disease","volume":"74","author":"Papazoglou","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30152-7","article-title":"Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (Sls II): A randomised controlled, double-blind, parallel group trial","volume":"4","author":"Tashkin","year":"2016","journal-title":"Lancet Respir Med"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903076","article-title":"Nintedanib for systemic sclerosis-associated interstitial lung disease","volume":"380","author":"Distler","year":"2019","journal-title":"N Engl J Med"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1002\/art.42075","article-title":"Nintedanib in patients with autoimmune disease-related progressive fibrosing interstitial lung diseases: Subgroup analysis of the Inbuild trial","volume":"74","author":"Matteson","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30318-0","article-title":"Tocilizumab in systemic sclerosis: A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"8","author":"Khanna","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B104","doi-asserted-by":"publisher","first-page":"2102347","DOI":"10.1183\/13993003.02347-2021","article-title":"Pirfenidone exacerbates Th2-driven vasculopathy in a mouse model of systemic sclerosis-associated interstitial lung disease","volume":"60","author":"Birnhuber","year":"2022","journal-title":"Eur Respir J"},{"key":"B105","doi-asserted-by":"publisher","first-page":"6458","DOI":"10.1038\/s41467-022-34145-4","article-title":"Single-cell profiling reveals distinct adaptive immune hallmarks in Mda5+ dermatomyositis with therapeutic implications","volume":"13","author":"Ye","year":"2022","journal-title":"Nat Commun"},{"key":"B106","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41584-023-01054-9","article-title":"Anti-Mda5 antibody-positive dermatomyositis: Pathogenesis and clinical progress","volume":"20","author":"Lu","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1002\/art.42264","article-title":"Two distinct immune cell signatures predict the clinical outcomes in patients with amyopathic dermatomyositis with interstitial lung disease","volume":"74","author":"Ye","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2025.100802","article-title":"Efficacy of Jak inhibitor combined with protein a immunoadsorption in Mda5+ dermatomyositis with Rpild: A real-world study","volume":"6","author":"Fu","year":"2025","journal-title":"Med"},{"key":"B109","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S2213-2600(22)00359-9","article-title":"Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): A double-blind, double-dummy, randomised, controlled, phase 2b trial","volume":"11","author":"Maher","year":"2023","journal-title":"Lancet Respir Med"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70226","article-title":"Monocyte-macrophage dynamics as key in disparate lung and peripheral immune responses in severe anti-melanoma differentiation-associated gene 5-positive dermatomyositis-related interstitial lung disease","volume":"15","author":"Shi","year":"2025","journal-title":"Clin Transl Med"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead273","article-title":"Increased Cd8+ tissue resident memory T cells, regulatory T cells and activated natural killer cells in systemic sclerosis lungs","volume":"63","author":"Padilla","year":"2024","journal-title":"Rheumatol (Oxford)"},{"key":"B112","doi-asserted-by":"crossref","DOI":"10.1101\/2025.08.07.669006","article-title":"Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease","volume-title":"Biorxiv","author":"Markov","year":"2025"},{"key":"B113","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1038\/s41467-023-36924-z","article-title":"Biased Il-2 signals induce Foxp3-rich pulmonary lymphoid structures and facilitate long-term lung allograft acceptance in mice","volume":"14","author":"Yamada","year":"2023","journal-title":"Nat Commun"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1002\/art.70066","article-title":"Single-cell analysis reveals peripheral helper T cells in rheumatoid arthritis-related interstitial lung disease","volume":"78","author":"Suga","year":"2026","journal-title":"Arthritis Rheumatol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.789740","article-title":"Oxidative stress promotes instability of regulatory T cells in antineutrophil cytoplasmic antibody-associated vasculitis","volume":"12","author":"Shimojima","year":"2021","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1882853\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:02:18Z","timestamp":1790258538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1882853\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":115,"alternative-id":["10.3389\/fimmu.2026.1882853"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1882853","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1882853"}}