1. Academic Validation
  2. Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Newborns

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Newborns

  • J Immunol. 2022 Jul 15;209(2):401-411. doi: 10.4049/jimmunol.2200142.
Dongmei Zhou 1 Meng Yao 1 Lijuan Zhang 1 Yingying Chen 1 Juan He 2 Yuxin Zhang 1 Haixu Xu 1 Pan Zhou 1 Wei Zhong 2 Zhi Yao 3 Jie Zhou 3
Affiliations

Affiliations

  • 1 Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; and.
  • 2 Guangzhou Women and Children's Medical Center, Guangzhou, China.
  • 3 Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; and zhoujie@tmu.edu.cn yaozhi@tmu.edu.cn.
Abstract

Necrotizing enterocolitis (NEC) is a common disorder in premature infants that is characterized by hyperinflammation and severe necrosis in the intestine. The pathogenesis of NEC remains to be elucidated. In this study, we demonstrate that adenosine, a metabolite more abundant in infants than in adults, plays an important role in the prevention of NEC. Administration of adenosine or its analog, adenosine-5'-N-ethyluronamide (NECA), dramatically relieved the severity of NEC in neonatal mice. Meanwhile, adenosine treatment significantly enhanced the immunosuppressive function, Antibacterial activity, and migration of myeloid-derived suppressor cells (MDSCs). However, depletion of MDSCs or inhibition of their migration using the CXCR2 Inhibitor SB225002 almost completely abrogated the protective effect of adenosine on NEC. Mechanistic studies showed that MDSCs in newborns expressed abundant Adenosine Receptor A2B (A2BR) that elicits intracellular cAMP signaling and its downstream target NF-κB. Importantly, intestinal tissues from patients with NEC showed significantly lower infiltration of A2BR-positive MDSCs than those from healthy donors. These observations revealed that adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.

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