{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:14:04Z","timestamp":1783433644829,"version":"3.54.6"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>More and more studies have shown that the immune system regulates the body\u2019s response to hypoxic stress. Immune dysregulation may increase vascular permeability, leading to edema and tissue damage, thereby causing high-altitude pulmonary edema (HAPE). Here, we found an increase in lung dendritic cells (DCs) in rat and mouse models of HAPE, but its specific role in HAPE remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, the function of rat lung DCs and its impact on T cells were analyzed through single-cell sequencing, flow cytometry and\n                      <jats:italic>in vitro<\/jats:italic>\n                      co-culture. Then, we confirmed its effects on DCs and T cells by intraperitoneal injection of TNF-\u03b1 or by using TNF-\u03b1 -deficient mice. Finally, we evaluated the role of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells in the progression of HAPE by eliminating CD4 in mice with neutralizing antibodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrated that hypobaric hypoxia (HH) induced the recruitment of pulmonary DCs in rats and promoted the immunosuppression of T cells (especially CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells). By injecting TNF-\u03b1 into rats, we found that the number of DC and CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      T cells in the lung of HH rats slightly decreased. Interestingly,\n                      <jats:italic>in vivo<\/jats:italic>\n                      injection of TNF-\u03b1 actually led to the production of less TNF-\u03b1 by CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells in the lung of HH rats. In the HAPE mouse model, the proportion and the number of DC in the lung of TNF-\u03b1 -deficient mice were significantly increased, and the level of IL-6 production was significantly decreased. Furthermore, the proportion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      T cells in the lung of TNF-\u03b1 -deficient mice increased significantly. By eliminating CD4 in mice with neutralizing antibodies, we found that CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells play a protective role in HAPE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results indicate that hypoxia induces the recruitment of DCs in the lung and mediates the differentiation of T cells into immunosuppressive phenotypes in HAPE rat and mouse models, thereby delaying the progression of HAPE. These findings highlight the potential approach of using immune regulation as a treatment for HAPE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1752864","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:25:58Z","timestamp":1774329958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypobaric hypoxia can lead to an increase in lung dendritic cells and promote T-cell immunosuppression, thereby preventing the excessive progression of high-altitude pulmonary edema"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuemei","family":"Wei","sequence":"first","affiliation":[{"name":"Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University","place":["Urumqi, China"]},{"name":"Center of Respiratory and Critical Care Medicine, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjiang Military Command","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjiang Military Command","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Kong","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Dong","sequence":"additional","affiliation":[{"name":"Center of Respiratory and Critical Care Medicine, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Respiratory and Critical Care Medicine, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziguli","family":"Maimaitituerxun","sequence":"additional","affiliation":[{"name":"Center of Respiratory and Critical Care Medicine, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congying","family":"Hou","sequence":"additional","affiliation":[{"name":"Center of Respiratory and Critical Care Medicine, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewei","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Respiratory and Critical Care Medicine, People\u2019s Hospital of Xinjiang Uygur Autonomous Region","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjiang Military Command","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0096-2016","article-title":"Acute high-altitude sickness","volume":"26","author":"Luks","year":"2017","journal-title":"Eur Respir Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1444666","article-title":"Whole transcriptome landscape in HAPE under the stress of environment at high altitudes: new insights into the mechanisms of hypobaric hypoxia tolerance","volume":"15","author":"Li","year":"2024","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2023.08.015","article-title":"High-altitude resident pulmonary edema induced by SARS-CoV-2 infection in children - A case series","volume":"135","author":"Mi","year":"2023","journal-title":"Int J Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s12890-024-02933-x","article-title":"Effect of furosemide in the treatment of high-altitude pulmonary edema","volume":"24","author":"Tenzing","year":"2024","journal-title":"BMC Pulm Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/1527029041352063","article-title":"Unraveling the mechanism of high altitude pulmonary edema","volume":"5","author":"Schoene","year":"2004","journal-title":"High Alt Med Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1378\/chest.92.5.814","article-title":"Clinical features of patients with high-altitude pulmonary edema in Japan","volume":"92","author":"Kobayashi","year":"1987","journal-title":"Chest"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.17.2228","article-title":"Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor","volume":"287","author":"Swenson","year":"2002","journal-title":"Jama"},{"key":"B8","article-title":"Exaggerated pulmonary hypertension is not sufficient to trigger high-altitude pulmonary oedema in humans","volume":"130","author":"Sartori","year":"2000","journal-title":"Schweiz Med Wochenschr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"111669","DOI":"10.1016\/j.biopha.2021.111669","article-title":"Polysaccharide from Potentilla anserina L ameliorate pulmonary edema induced by hypobaric hypoxia in rats","volume":"139","author":"Shi","year":"2021","journal-title":"BioMed Pharmacother"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3181\/0712-RM-337","article-title":"Role of oxidative stress and NFkB in hypoxia-induced pulmonary edema","volume":"233","author":"Sarada","year":"2008","journal-title":"Exp Biol Med Maywood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-015-0491-3","article-title":"Hypoxia-induced inflammatory chemokines in subjects with a history of high-altitude pulmonary edema","volume":"31","author":"Mishra","year":"2016","journal-title":"Indian J Clin Biochem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13461","article-title":"Deregulated hypoxic response in myeloid cells: A model for high-altitude pulmonary oedema (HAPE)","volume":"229","author":"Gojkovic","year":"2020","journal-title":"Acta Physiol Oxf"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012656","article-title":"Inflammation in pulmonary hypertension and edema induced by hypobaric hypoxia exposure","volume":"23","author":"El Alam","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910701","article-title":"Chronic and cycling hypoxia: drivers of cancer chronic inflammation through HIF-1 and NF-\u03baB activation: A review of the molecular mechanisms","volume":"22","author":"Korbecki","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020843","article-title":"The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors-A review of literature","volume":"22","author":"Korbecki","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/j.immuni.2023.07.001","article-title":"Dendritic cell type 3 arises from Ly6C(+) monocyte-dendritic cell progenitors","volume":"56","author":"Liu","year":"2023","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","first-page":"112793","DOI":"10.1016\/j.celrep.2023.112793","article-title":"Cross-organ single-cell transcriptome profiling reveals macrophage and dendritic cell heterogeneity in zebrafish","volume":"42","author":"Zhou","year":"2023","journal-title":"Cell Rep"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1016\/j.immuni.2024.05.007","article-title":"Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells","volume":"57","author":"Rodrigues","year":"2024","journal-title":"Immunity"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90591.2008","article-title":"Sustained hypoxia promotes the development of a pulmonary artery-specific chronic inflammatory microenvironment","volume":"297","author":"Burke","year":"2009","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400338RR","article-title":"Classical dendritic cells contribute to hypoxia-induced pulmonary hypertension","volume":"38","author":"Mickael","year":"2024","journal-title":"FASEB J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.20914","article-title":"High-soluble-fiber diet attenuates hypoxia-induced vascular remodeling and the development of hypoxic pulmonary hypertension","volume":"80","author":"Pakhomov","year":"2023","journal-title":"Hypertension"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06409-6","article-title":"Lactate limits CNS autoimmunity by stabilizing HIF-1\u03b1 in dendritic cells","volume":"620","author":"Sanmarco","year":"2023","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1080\/01902148.2025.2515361","article-title":"Hypobaric hypoxia promotes the production of IL-10 of lung NKT cells in HAPE rats to fight inflammation","volume":"51","author":"Li","year":"2025","journal-title":"Exp Lung Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/sji.13159","article-title":"Single-cell RNA sequencing distinguishes dendritic cell subsets in the rat, allowing advanced characterization of the effects of FMS-like tyrosine kinase 3 ligand","volume":"96","author":"Carlson","year":"2022","journal-title":"Scand J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5474","article-title":"The chemokine CCL6 promotes innate immunity via immune cell activation and recruitment","volume":"179","author":"Coelho","year":"2007","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.immuni.2025.01.003","article-title":"Dichgans M. A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis","volume":"58","author":"Asare","year":"2025","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.987394","article-title":"EPSTI1 as an immune biomarker predicts the prognosis of patients with stage III colon cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1139\/bcb-2021-0284","article-title":"Working from within: how secretory leukocyte protease inhibitor regulates the expression of pro-inflammatory genes","volume":"100","author":"Douglas","year":"2022","journal-title":"Biochem Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00276.2012","article-title":"FABP5 deficiency enhances susceptibility to H1N1 influenza A virus-induced lung inflammation","volume":"305","author":"Gally","year":"2013","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12935-022-02698-5","article-title":"Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma","volume":"22","author":"Xiong","year":"2022","journal-title":"Cancer Cell Int"},{"key":"B31","doi-asserted-by":"publisher","first-page":"15103","DOI":"10.1038\/s41598-023-42184-0","article-title":"Exploring shared pathways and the shared biomarker ERRFI1 in Obstructive sleep apnoea and atherosclerosis using integrated bioinformatics analysis","volume":"13","author":"Chen","year":"2023","journal-title":"Sci Rep"},{"key":"B32","doi-asserted-by":"publisher","first-page":"115715","DOI":"10.1016\/j.intimp.2025.115715","article-title":"The synapse revisited: Molecular networks of CD4 T cell-DC interactions","volume":"167","author":"Bonilha","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-024-02005-9","article-title":"TNF-\u03b1 and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema","volume":"29","author":"Ge","year":"2024","journal-title":"Apoptosis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.2533-23","article-title":"Clinical and pathophysiological features of high-altitude pulmonary edema in the Japanese population: A review of studies on high-altitude pulmonary edema in Japan","volume":"63","author":"Hanaoka","year":"2024","journal-title":"Intern Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/thx.51.7.739","article-title":"Cytokines in bronchoalveolar lavage fluid in patients with high altitude pulmonary oedema at moderate altitude in Japan","volume":"51","author":"Kubo","year":"1996","journal-title":"Thorax"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(98)00006-1","article-title":"Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema","volume":"111","author":"Kubo","year":"1998","journal-title":"Respir Physiol"},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.1001\/jama.1986.03380010067027","article-title":"High-altitude pulmonary edema. Characteristics of lung lavage fluid","volume":"256","author":"Schoene","year":"1986","journal-title":"Jama"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.64.6.2605","article-title":"The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema","volume":"64","author":"Schoene","year":"1988","journal-title":"J Appl Physiol 1985"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0644(87)80745-X","article-title":"High-altitude pulmonary edema: pathophysiology and clinical review","volume":"16","author":"Schoene","year":"1987","journal-title":"Ann Emerg Med"},{"key":"B40","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V90.4.1458","article-title":"CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha: II. Functional analysis","volume":"90","author":"Caux","year":"1997","journal-title":"Blood"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0116","article-title":"Development and activation of human dendritic cells in vivo in a xenograft model of human hematopoiesis","volume":"23","author":"Cravens","year":"2005","journal-title":"Stem Cells"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03176","article-title":"Human dendritic cells: their heterogeneity and clinical application potential in cancer immunotherapy","volume":"9","author":"Patente","year":"2018","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic instruction of immunity","volume":"169","author":"Buck","year":"2017","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"8605471","DOI":"10.1155\/2018\/8605471","article-title":"Regulation of immune cell functions by metabolic reprogramming","volume":"2018","author":"Kim","year":"2018","journal-title":"J Immunol Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1038\/s41467-019-10015-4","article-title":"Competition for nutrients and its role in controlling immune responses","volume":"10","author":"Kedia-Mehta","year":"2019","journal-title":"Nat Commun"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/cells14100736","article-title":"Physiological oxygen levels in the microenvironment program ex vivo-generated conventional dendritic cells toward a tolerogenic phenotype","volume":"14","author":"Peter","year":"2025","journal-title":"Cells"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.11.003","article-title":"When oxygen runs short: the microenvironment drives host-pathogen interactions","volume":"14","author":"Dietz","year":"2012","journal-title":"Microbes Infect"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0910283","article-title":"Hypoxia and inflammation","volume":"364","author":"Eltzschig","year":"2011","journal-title":"N Engl J Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0244366","article-title":"Hypoxia-inducible factor 1 alpha limits dendritic cell stimulation of CD8 T cell immunity","volume":"15","author":"Tran","year":"2020","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142053","article-title":"Influence of hypoxia-inducible factor 1\u03b1 on dendritic cell differentiation and migration","volume":"42","author":"K\u00f6hler","year":"2012","journal-title":"Eur J Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-07-0391","article-title":"Transcriptome of hypoxic immature dendritic cells: modulation of chemokine\/receptor expression","volume":"6","author":"Ricciardi","year":"2008","journal-title":"Mol Cancer Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0208082","article-title":"Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile","volume":"84","author":"Elia","year":"2008","journal-title":"J Leukoc Biol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1111\/imm.13893","article-title":"Newly found rat CD103 (-) dendritic cells represent a highly immunogenic subpopulation of type-2 conventional dendritic cells, corresponding to known dendritic cell subsets in mice and humans","volume":"174","author":"Sawanobori","year":"2025","journal-title":"Immunology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s12931-025-03370-y","article-title":"Single-cell landscape of mouse lungs exposed to intermittent hypoxia","volume":"26","author":"Zheng","year":"2025","journal-title":"Respir Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"3500","DOI":"10.1038\/s41598-018-21891-z","article-title":"HIF-1\u03b1 hampers dendritic cell function and Th1 generation during chronic visceral leishmaniasis","volume":"8","author":"Hammami","year":"2018","journal-title":"Sci Rep"},{"key":"B56","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13045-022-01292-6","article-title":"Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape","volume":"15","author":"Wu","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1182\/bloodadvances.2016000984","article-title":"Adenosine signaling mediates hypoxic responses in the chronic lymphocytic leukemia microenvironment","volume":"1","author":"Serra","year":"2016","journal-title":"Blood Adv"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00698","article-title":"Th17 polarization under hypoxia results in increased IL-10 production in a pathogen-independent manner","volume":"8","author":"Volchenkov","year":"2017","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-91287-5_27","article-title":"Hypoxia-\/HIF-1\u03b1-driven factors of the tumor microenvironment impeding antitumor immune responses and promoting Malignant progression","volume":"1072","author":"Vaupel","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1080\/10520295.2018.1556806","article-title":"Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors","volume":"94","author":"Kouvaras","year":"2019","journal-title":"Biotech Histochem"},{"key":"B61","doi-asserted-by":"publisher","first-page":"13110","DOI":"10.1038\/srep13110","article-title":"Development of PD-1\/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer","volume":"5","author":"He","year":"2015","journal-title":"Sci Rep"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.12082","article-title":"VEGF-A is associated with the degree of TILs and PD-L1 expression in primary breast cancer","volume":"34","author":"Fujii","year":"2020","journal-title":"In Vivo"},{"key":"B63","doi-asserted-by":"publisher","first-page":"61","DOI":"10.32607\/actanaturae.27393","article-title":"LPS-induced acute lung injury: analysis of the development and suppression by the TNF-\u03b1-targeting aptamer","volume":"16","author":"Sen\u2019kova","year":"2024","journal-title":"Acta Naturae"},{"key":"B64","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1186\/s12931-024-02975-z","article-title":"Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response","volume":"25","author":"Yang","year":"2024","journal-title":"Respir Res"},{"key":"B65","doi-asserted-by":"publisher","first-page":"155591","DOI":"10.1016\/j.phymed.2024.155591","article-title":"Syringic acid attenuates acute lung injury by modulating macrophage polarization in LPS-induced mice","volume":"129","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"B66","doi-asserted-by":"publisher","first-page":"119207","DOI":"10.1016\/j.jep.2024.119207","article-title":"Huashi baidu granule alleviates inflammation and lung edema by suppressing the NLRP3\/caspase-1\/GSDMD-N pathway and promoting fluid clearance in a porcine reproductive and respiratory syndrome (PRRS) model","volume":"340","author":"Zhang","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00051.2016","article-title":"Selective HDAC6 inhibition prevents TNF-\u03b1-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema","volume":"311","author":"Yu","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"113982","DOI":"10.1016\/j.biopha.2022.113982","article-title":"Eleutheroside B ameliorated high altitude pulmonary edema by attenuating ferroptosis and necroptosis through Nrf2-antioxidant response signaling","volume":"156","author":"Wang","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1113\/JP288584","article-title":"Distinct immune cell profiles associated with high-altitude hypoxia and severe acute mountain sickness","author":"Han","year":"2025","journal-title":"J Physiol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"31574","DOI":"10.1038\/s41598-025-15175-6","article-title":"Targeting dendritic cell-specific TNFR2 improves skin and joint inflammation in a murine model of psoriatic arthritis","volume":"15","author":"Kaur","year":"2025","journal-title":"Sci Rep"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136071","article-title":"Molecular signatures of dendritic cell activation upon TNF stimulation: A multi-omics study in rheumatoid arthritis","volume":"26","author":"Alshevskaya","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B72","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41419-025-08214-7","article-title":"TRIP13 promotes the expansion and immunosuppression of CD4(+)Foxp3(+) regulatory T cells by sustaining HAT1 stability","volume":"17","author":"He","year":"2026","journal-title":"Cell Death Dis"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1038\/s41467-025-57668-y","article-title":"Alveolar macrophages from persons with HIV mount impaired TNF signaling networks to M. tuberculosis infection","volume":"16","author":"Kgoadi","year":"2025","journal-title":"Nat Commun"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.08.032","article-title":"Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14+ macrophages","volume":"141","author":"Atreya","year":"2011","journal-title":"Gastroenterology"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S401293","article-title":"Berberine alleviates acute lung injury in septic mice by modulating treg\/th17 homeostasis and downregulating NF-\u03baB signaling","volume":"17","author":"Chen","year":"2023","journal-title":"Drug Des Devel Ther"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.09.053","article-title":"Multi-immunometabolomics mining: NP prevents hyperimmune in ALI by inhibiting Leucine\/PI3K\/Akt\/mTOR signaling pathway","volume":"225","author":"Zhao","year":"2024","journal-title":"Free Radic Biol Med"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.24976\/Discov.Med.202436191.223","article-title":"Hyperbaric oxygen protects acute lung injury secondary to deinagkistrodon acutus venom poisoning by regulating th17\/treg balance","volume":"36","author":"Li","year":"2024","journal-title":"Discov Med"},{"key":"B78","doi-asserted-by":"publisher","first-page":"L750","DOI":"10.1152\/ajplung.00251.2019","article-title":"Delayed Akt suppression in the lipopolysaccharide-induced acute lung injury promotes resolution that is associated with enhanced effector regulatory T cells","volume":"318","author":"Artham","year":"2020","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"106369","DOI":"10.1016\/j.intimp.2020.106369","article-title":"Blockade of interleukin-2-inducible T-cell kinase signaling attenuates acute lung injury in mice through adjustment of pulmonary Th17\/Treg immune responses and reduction of oxidative stress","volume":"83","author":"Nadeem","year":"2020","journal-title":"Int Immunopharmacol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1752864\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:26:00Z","timestamp":1774329960000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1752864\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":79,"alternative-id":["10.3389\/fimmu.2026.1752864"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1752864","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"article-number":"1752864"}}