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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1465938
This article is part of the Research Topic Unraveling the Molecular Mechanisms of Cytokine Signaling in Regulating Inflammatory Diseases View all 13 articles

Myeloid-derived growth factor promotes M2 macrophage polarization and attenuates Sjögren's syndrome via suppression of the CX3CL1/CX3CR1 axis

Provisionally accepted
Zi Yang Zi Yang Mangnan Liu Mangnan Liu *Zhichao Chang Zhichao Chang *Conglin Du Conglin Du *Yang Yang Yang Yang *Chen Zhang Chen Zhang *Liang Hu Liang Hu *
  • Capital Medical University, Beijing, China

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

    Introduction: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells into the salivary galands. The re-establishment of salivary gland (SG) function in pSS remains a clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities. However, the potential of MYDGF to restore salivary glands (SGs) function during pSS has not yet been investigated. Methods: Non-obese diabetic (NOD)/Ltj mice (pSS model) were intravenously administered with adeno-associated viruses of MYDGF at 11 weeks of age. Salivary flow rates were determined before and after treatment. Mice were sacrificed 5 weeks after MYDGF treatment, and submandibular glands were collected for analyses of histological disease scores, inflammatory cell infiltration, PCR determination of genes, and western blotting of functional proteins. Furthermore, mRNA sequencing and bioinformatics predicted the mechanism of the therapeutic effect of MYDGF. Results: Treatment of NOD/Ltj mice with MYDGF alleviated pSS, as indicated by the increased salivary flow rate, reduced lymphocyte infiltration, attenuated glandular inflammation, and increased AQP5 and NKCC1 expression. The gene expression of cytokines and chemokines, such as Ccl12, Ccl3, Il1r1, Ccr2, Cx3cr1, Il7, Mmp2, Mmp14, Il1b, and Il7, significantly decreased after treatment with MYDGF, as determined by RNA sequencing. Meanwhile, MYDGF inhibits infiltration of macrophages (Mϕ) in SGs, induces polarization of M2ϕ, and suppresses C-X3C motif ligand 1 (CX3CL1)/C-X3C motif receptor 1 (CX3CR1) axis. Conclusions: Our findings showed that MYDGF could revitalize the SG function of pSS, inhibit infiltration of Mϕ, and promote M2ϕ polarization via suppression of the CX3CL1/CX3CR1 axis, which has implications for potential therapy for pSS.

    Keywords: Sjögren's syndrome, Salivary Glands, Myeloid-derived growth factor, M2 macrophage polarization, CX3CL1, CX3CR1

    Received: 17 Jul 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Yang, Liu, Chang, Du, Yang, Zhang and Hu. 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:
    Mangnan Liu, Capital Medical University, Beijing, China
    Zhichao Chang, Capital Medical University, Beijing, China
    Conglin Du, Capital Medical University, Beijing, China
    Yang Yang, Capital Medical University, Beijing, China
    Chen Zhang, Capital Medical University, Beijing, China
    Liang Hu, Capital Medical University, Beijing, China

    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.