Kim, Hyelim Park, Hee Ho Kim, Hong Nam Seo, Donghyuk Hong, Kyung Soo Jang, Jong Geol Seo, Eun U. Kim, In- Young Jeon, So- Young Son, Boram Cho, Seong-Woo Kim, Wantae Ahn, June Hong Lee, Wonhwa 2024-07-11T06:01:17Z 2024-07-11T06:01:17Z 2024-07-11 2024-06 0027-8424 https://pubs.kist.re.kr/handle/201004/150215 Thymocyte selection-associated high - mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2) infection by binding to the cell surface receptor for advanced glycation end - products (RAGE). In various diseases, including COVID - 19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX - induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX - mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS. English National Academy of Sciences The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases Article 10.1073/pnas.2319322121 1 Proceedings of the National Academy of Sciences of the United States of America, v.121, no.26 Proceedings of the National Academy of Sciences of the United States of America 121 26 Y scie scopus 001255969400004 2-s2.0-85196905228 Multidisciplinary Sciences Science & Technology - Other Topics Article CELL RECEPTOR SEPSIS HMGB1 TOX RAGE severe COVID-19 septic shock fibroproliferative ARDS