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Liao, Y.* ; Liu, Y.* ; Yang, R.* ; Zhu, Z.* ; Wu, J.* ; Li, D.* ; Su, J.* ; He, Y.* ; Luo, S. ; Cao, F.* ; Deng, H.* ; Yang, L.* ; Zhong, L.* ; Peng, P.* ; Wu, X.* ; Cai, C.* ; Li, Z.* ; Wu, Y.* ; Zhu, S.* ; Wei, J.* ; Yang, Y.* ; Wang, L.*

IL-7R-enriched extracellular vesicles from the thymus drive colitis via promoting neutrophil extracellular trap formation.

Adv. Sci.:e20331 (2026)

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Mounting evidence highlights the involvement of extra-intestinal organs in inflammatory bowel disease (IBD) progression, yet the mechanisms underlying gut-extraintestinal organ crosstalk remain poorly understood. Extracellular vesicles (EVs) serve as pivotal mediators of inter-organ communication. Here, this study demonstrates that circulating EVs from colitis exacerbate colitis severity by inducing neutrophil extracellular trap (NET) formation. Inhibition of circulating EV secretion or NET formation alleviates colitis severity. Mechanistically, EVs enriched with interleukin-7 receptor (IL-7R) are identified as critical drivers of NET-mediated colitis exacerbation. Downregulation of IL-7R ameliorates colitis symptoms, whereas IL-7R upregulation worsens disease progression. IL-7R is found to induce NETs via the protein-arginine deiminase type 4 (PAD4) pathway to aggravate colitis. Furthermore, this study establishes that thymus-derived EVs are the primary source of IL-7R-enriched circulating EVs. During colitis, elevated circulating lipopolysaccharide (LPS) stimulates the thymus to release IL-7R-enriched EVs, which then migrate via the thymus-gut axis and promote NET formation in colonic tissues. This study reveals a previously unrecognized thymus-gut communication axis mediated by IL-7R-enriched EVs in IBD pathogenesis and provides an explanation for why IBD predominantly affects children and young adults. Targeting this axis may offer novel therapeutic strategies for IBD management.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Il‐7r‐enriched Extracellular Vesicles ; Inflammatory Bowel Disease ; Neutrophil Extracellular Traps, Thymus‐gut Axis

ISSN (print) / ISBN 2198-3844

e-ISSN 2198-3844

Journal Advanced science

Quellenangaben Article Number: e20331

Publisher Wiley

Publishing Place Weinheim

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)

Grants Open Project of Guangzhou Medical University