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. 2025 Jun 24.
doi: 10.1007/s10620-025-09135-3. Online ahead of print.

Targeting TREM1 Ameliorates Necrotizing Enterocolitis in Neonatal Mice by Inhibiting Endoplasmic Reticulum Stress and Regulating Macrophage Polarization

Xiaolei Xie  1 , Binbin Qiu  1 , Jin Huang  2
Affiliations

Targeting TREM1 Ameliorates Necrotizing Enterocolitis in Neonatal Mice by Inhibiting Endoplasmic Reticulum Stress and Regulating Macrophage Polarization

Xiaolei Xie et al. Dig Dis Sci. .

Abstract

Objective: This study aims to investigate the role of TREM1 in necrotizing enterocolitis (NEC).

Methods: A mouse model of NEC was established through artificial feeding combined with hypoxia-cold stress. Intestinal injury was assessed via H&E staining. Inflammatory cytokines were measured by ELISA, and reactive oxygen species (ROS) activity was evaluated using DHE staining. Intestinal permeability was determined by the fluorescein-isothiocyanate-dextran (FITC-dextran) method. Tight junction proteins were analyzed through immunohistochemistry and western blotting. The expression of CD86 and CD206 in M1 and M2 macrophages was assessed by immunofluorescence, and the mRNA levels of M1 and M2 markers (CD86, iNOS, CD206, and Arg-1) were detected by RT-qPCR. Proteins involved in ER stress were analyzed using western blotting.

Results: Inhibition of TREM1 was found to reduce intestinal injury, inflammation, and oxidative stress, improve intestinal barrier function, suppress M1 macrophage polarization, and attenuate ER stress in NEC mice. Moreover, we found that treatment with the ER stress inducer tunicamycin reversed these protective effects of TREM1 inhibition.

Conclusion: TREM1 inhibition protects against intestinal injury, inflammation, oxidative stress, intestinal barrier damage, and M1 macrophage polarization in NEC mice by suppressing ER stress.

Keywords: ER stress; Macrophage polarization; Necrotizing enterocolitis; TREM1.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The authors are responsible for the integrity and accuracy of this study. All animal procedures were conducted in accordance with the ARRIVE guidelines and the NIH Guide for the Care and Use of Laboratory Animals.

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