2. Academic Validation
  3. T Cell-Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1

T Cell-Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1

  • Adv Sci (Weinh). 2024 Jun 18:e2401634. doi: 10.1002/advs.202401634.
Yang Zhou 1 2,  Lili Bao 2,  Shengkai Gong 2,  Geng Dou 2,  Zihan Li 2,  Zhengyan Wang 3,  Lu Yu 4,  Feng Ding 2 5,  Huan Liu 6,  Xiayun Li 1,  Siying Liu 7,  Xiaoshan Yang 2 8,  Shiyu Liu 2
Affiliations

Affiliations

  • 1 College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 3 Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, China.
  • 4 Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, China.
  • 5 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Radiology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 6 Department of Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100871, China.
  • 7 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 8 Stomatology Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China.
PMID: 38888507 DOI: 10.1002/advs.202401634
Abstract

Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell-derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2'3' cyclic GMP-AMP (cGAMP) and activates Cyclic GMP-AMP Synthase (cGAS)-stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS-STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

Keywords

ENPP1; apoptotic extracellular vesicles; cGAMP, cGAS‐STING pathway; radiation enteritis.

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