Skip to main content

BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1480675
This article is part of the Research Topic Community Series in The Role of Monocytes/Macrophages in Autoimmunity and Autoinflammation: Volume II View all 3 articles

Possible involvement of Toll-like receptor 8-positive monocytes/macrophages in the pathogenesis of Sjögren's disease

Provisionally accepted
Lijing Yan Lijing Yan Yuka Miyahara Yuka Miyahara Mizuki Sakamoto Mizuki Sakamoto Naoki Kaneko Naoki Kaneko *Hu Chen Hu Chen Junsei Sameshima Junsei Sameshima Hajime Kido Hajime Kido Shiho Yokomizo Shiho Yokomizo Tomoki Sueyoshi Tomoki Sueyoshi Haruki Nagano Haruki Nagano Yukiko Ohyama Yukiko Ohyama Seiji Nakamura Seiji Nakamura Shintaro Kawano Shintaro Kawano Masafumi Moriyama Masafumi Moriyama *
  • Kyushu University Hospital, Fukuoka, Japan

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

    Background: Sjögren's disease (SjD) is an autoimmune disease marked by lymphocytic infiltration of salivary and lacrimal glands, leading to glandular dysfunction, where CD4-positive helper T (Th) cells and their cytokines are crucial in the pathogenesis. Recent studies have demonstrated that Tolllike receptors (TLRs), particularly those recognizing immune complexes containing DNA and RNA, contribute to Th cell activation in various autoimmune diseases. This study explores the expression and function of these TLRs in SjD.Methods: DNA microarray analysis of salivary gland tissue from six SjD patients and real-time PCR (n = 32) was used to identify overexpressed TLRs. Single-cell RNA sequencing (scRNA-seq) was performed using tissue lesions and integrated with published scRNA-seq data from tissues and peripheral blood mononuclear cells to examine gene expression in macrophages and monocytes.Finally, multi-color immunofluorescence staining was conducted to confirm TLR8 expression and function in SjD lesions (n = 19).Results: DNA microarray analysis revealed the up-regulation of TLR8, along with other TLRs and innate immune response genes in SjD. Real-time PCR showed significant up-regulation of TLR7 and TLR8. TLR8 up-regulated in both analyses. In scRNA-seq analysis, the TLR8-expressing cluster comprised macrophages and monocytes, which also produced T cell activation genes like CD86.TLR8-positive macrophages infiltrated inflammatory sites and frequently expressed CD86 in quantitative imaging approaches.Conclusions: These results suggest that infiltrating monocytes and macrophages may produce cytokines and chemokines through TLR8 stimulation, potentially enhancing B7 molecule expression, promoting the adaptive immune response, and contributing to SjD pathogenesis.

    Keywords: Sjögren's disease, Toll-Like Receptor 8, monocyte, macrophage, CD86

    Received: 14 Aug 2024; Accepted: 10 Oct 2024.

    Copyright: © 2024 Yan, Miyahara, Sakamoto, Kaneko, Chen, Sameshima, Kido, Yokomizo, Sueyoshi, Nagano, Ohyama, Nakamura, Kawano and Moriyama. 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:
    Naoki Kaneko, Kyushu University Hospital, Fukuoka, Japan
    Masafumi Moriyama, Kyushu University Hospital, Fukuoka, Japan

    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.