REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Renal Macrophage TLR7 Signaling in Lupus Nephritis: From Pathogenic Mechanisms to Therapeutic Opportunities
Longzhu Li 1
Zeqiong Lin 1
LU Chen 1
Junmin Huang 1
Hongying Luo 1
Ziqian Bi 2
Tianyang Wang 3
Yongzhi Xu 1
Huafeng Liu 1
Junfeng Hao 1
Jiansong QI 1
1. Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
2. Purdue University, West Lafayette, United States
3. Xi'an Jiaotong-Liverpool University, Suzhou, China
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Abstract
Recent studies, including reports of rare monogenic Toll-Like Receptor 7 (TLR7) gain-of-function mutations, have established TLR7 as a causal driver in a subset of human systemic lupus erythematosus (SLE) cases. Consequently, TLR7 and its downstream mediators have emerged as promising therapeutic targets. Beyond its role in B cells, TLR7 is also critical within the renal tissue of patients with lupus nephritis (LN), where single strand RNA (ssRNA) drives aberrant TLR7 activation in macrophages. This activation promotes robust inflammatory cytokines production, exacerbating autoantigen generation and inflammatory tissue damage in a self-reinforcing feedback loop that accelerates LN progression. This review explores the role of TLR7 in LN pathogenesis through the lens of macrophage biology, with the goal of identifying novel therapeutic strategies that modulate the TLR7 signaling pathway.
Summary
Keywords
Endolysosomal TLR7 signaling blockade, Lupus Nephritis, Lysosomal Regulation, Macrophages, Toll-Like Receptor 7
Received
27 December 2025
Accepted
17 February 2026
Copyright
© 2026 Li, Lin, Chen, Huang, Luo, Bi, Wang, Xu, Liu, Hao and QI. 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: Huafeng Liu; Junfeng Hao; Jiansong QI
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.