Renal macrophage TLR7 signaling in lupus nephritis: from pathogenic mechanisms to therapeutic opportunities

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.