Interleukin 16 in lupus nephritis-a role for Th1 and CD8+ T cell migration.

Dysregulation of interleukin (IL) 16 has been implicated in SLE, yet its cellular source and role in disease pathogenesis remain unclear. We analysed circulating IL16+ immune cells from 40 SLE patients, including 32 with active disease (SLEDAI-2K ≥ 4) using spectral flow cytometry. Plasma (pIL16) and urine IL16 (uIL16) levels were measured, and correlations with clinical variables were assessed. IL16 effects on T cell migration were studied in vitro. Active SLE patients showed broadly reduced proportions of cells expressing IL16, including CD4+T, CD8+T, B, and NK cells. This reduction was prominent in several cell subsets including Th1-like cells and plasmablasts. Further sub-analyses of lupus nephritis (LN) versus non-LN, demonstrated significantly reduced IL16 expression e.g., in Th1-like and double negative B cell subsets in LN. In parallel, SLE patients displayed increased pIL16 levels, and LN patients showed increased uIL16 which associated positively with disease activity SLEDAI-2K index and negatively with complement C4 levels and IL16+CD4+T-cell counts. In vitro, IL16 induced CXCR4 and CCR5 mediated migration of Th1-cells and attracted CD8+T cells via CXCR4, which was partially inhibited by IL16 blockade. We demonstrate reduced intracellular IL16 expression in SLE lymphocytes, with low IL16+CD4+T cell proportions in LN correlating with increased uIL16. Extracellular IL16 may drive Th1 and CD8+T cell infiltration, contributing to organ inflammation. IL16 blockade reduced T cell migration, highlighting its potential as therapeutic target.