Anti-IL-10R antibody reveals IL-10 modestly limits TLR7-induced lupus progression in mice, primarily via CD4 T-cells.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease driven by dysregulated innate and adaptive immunity, leading to chronic inflammation. Interleukin-10 (IL-10), typically an anti-inflammatory cytokine, exhibits inconsistent dual pro- and anti-inflammatory roles in SLE, promoting B cell differentiation and autoantibody production in some contexts. This variability, likely due to differences in disease context and microenvironment, creates a significant gap in understanding its therapeutic potential and biomarker utility.

Researchers investigated IL-10's role in a toll-like receptor 7 (TLR7) agonist-induced murine model of lupus. They administered an antagonistic anti-IL-10 receptor (anti-IL-10R) antibody to clarify its broad in vivo effects. The study assessed the progression of lupus-like features and associated immune changes, focusing on the CD4 T-cell compartment. Subsequently, they examined the underlying signaling pathways, including STAT3, to elucidate observed immune alterations.

IL-10 exhibited both pro- and anti-inflammatory effects on immune cells; however, overall, it modestly limited disease progression, suggesting its regulatory actions slightly outweighed pro-inflammatory ones under the study conditions. The most pronounced effects were observed within the CD4 T-cell compartment. > IL-10R blockade increased IL-17 expression while reducing regulatory T cell (Treg) frequencies, IL-10 expression, and slightly also interferon gamma (IFN-γ) expression. Mechanistically, IL-10 activated similar downstream pathways in T effector cells (CD4+FoxP3- Teff) and CD4+FoxP3+ Treg, with signal transducer and activator of transcription 3 (STAT3) signaling being most prominent. The heightened sensitivity of Tregs to IL-10R blockade was speculated to stem from slightly elevated IL-10R expression on these cells.