김홍남 (한국과학기술연구원(KIST)) | 한빛사논문 > 한빛사

한빛사논문

조회289

한국과학기술연구원(KIST)

CV File 233 kb

Proc. Natl. Acad. Sci. USA, Jun 25 2024, 121 (26) | https://doi.org/10.1073/pnas.2319322121 The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases

Hyelim Kim^a,b,1, Hee Ho Park^c,d,1, Hong Nam Kim^a,e,f,g,1, Donghyuk Seo^h, Kyung Soo Hongⁱ, Jong Geol Jangⁱ, Eun U Seo^a,e, In-Young Kim^j, So-Young Jeon^j, Boram Son^c, Seong-Woo Cho^b, Wantae Kim^j,2, June Hong Ahn^i,2, and Wonhwa Lee^h,2

^aBrain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea;

^bDepartment of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea;

^cDepartment of Bioengineering, Hanyang University, Seoul 04763, Republic of Korea;

^dResearch Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea;

^eDivision of Bio-Medical Science and Technology (Korea Institute of Science and Technology School), Korea University of Science and Technology, Seoul 02792, Republic of Korea;

^fSchool of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea;

^gYonsei-Korea Institute of Science and Technology Convergence Research Institute, Yonsei University, Seoul 03722, Republic of Korea;

^hDepartment of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea;

ⁱDivision of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu 42415, Republic of Korea; and

^jDepartment of Life Science, University of Seoul, Seoul 02504, Republic of Korea

¹H.K., H.H.P., and H.N.K. contributed equally to this work.

²To whom correspondence may be addressed. : Wantae Kim, June Hong Ahn, Wonhwa Lee

Abstract

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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-23)
연구진국내 연구진
분야 생명과학 > 면역학

댓글 작성 로그인

CV 열람하기

연락처 보기