Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Nutritional Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1501307
This article is part of the Research Topic Stress, Immunity, and Inflammation in Metabolic Disorders View all articles

Siglec-E augments adipose tissue inflammation by modulating TRAF3 signaling and monocytic myeloid-derived suppressor cells during obesity

Provisionally accepted

The final, formatted version of the article will be published soon.

    Background. Obesity is associated with dysregulated metabolism and low-grade chronic inflammation in adipose tissue (AT). Immune cells, including macrophages, T cells, and neutrophils, infiltrate the AT and secrete proinflammatory cytokines to exacerbate the AT inflammation. RNA-Seq analysis of AT immune cells isolated from mice fed a high-fat diet (HFD) versus normal fat diet (NFD) identified a panel of genes that were markedly downregulated, including sialic acid-binding Ig-like lectin E (siglec-E), in HFD compared to NFD mice.A series of experiments in wild-type (WT) and siglec-E knockout (siglec-E KO) mice was designed to investigate the effect of HFD on the functional role of siglec-E in the regulation of AT inflammation and adipogenesis. We analyzed the changes in immune phenotypes, inflammatory response, adipogenesis, and levels of cytokines and chemokine after HFD and ND feeding.. HFD consumption significantly increased the body weight and blood glucose levels in siglec-E KO mice relative to those of WT mice. This was associated with an increased infiltration of macrophages, CXCR3 expressing CD8 T cells, and monocytic myeloid-derived suppressor cells (M-MDSCs) with a concomitant decrease in numbers of dendritic cells (DCs), in the AT of siglec-E KO fed HFD versus the WT HFD counterparts. The HFD-fed siglec-E KO mice also exhibited elevated expression of intracellular Akt and TNF receptor-associated factor 3 (TRAF3) signaling, inducing C/EBPα, FASN, PPARg, and resistin in suprascapular AT compared to WT HFD-fed mice. Taken together, these results suggest that a genetic deficiency of siglec-E plays a key role in inducing AT inflammation by differentially altering M-MDSCs and CD8 + CXCR3 + T cell function and adipogenesis by TRAF3 and Akt signaling in AT.Our findings strongly suggest that modulation of siglec-E pathways might have a protective effect at least in part against AT inflammation and metabolic disorders.

    Keywords: Adipose Tissue, CXCR3, MDSCs, Siglec-E, TRAF3

    Received: 24 Sep 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Rakib, Mandal, Al Mamun, Kiran, Yasmen, Li, Collier, Jiang, Park and Singh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Udai P Singh, University of Tennessee Health Science Center (UTHSC), Memphis, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.