# Interleukin 16 in lupus nephritis—a role for Th1 and CD8+ T cell migration

## TL;DR

This study explores how interleukin 16 (IL16) affects immune cells in lupus patients, finding that low IL16 in certain cells correlates with higher disease activity and kidney inflammation.

## Contribution

The study identifies IL16's role in T cell migration and its potential as a therapeutic target in lupus nephritis.

## Key findings

- Active SLE patients have reduced intracellular IL16 in immune cells like CD4+T, CD8+T, B, and NK cells.
- Lupus nephritis patients show increased urine IL16 levels linked to higher disease activity and lower complement C4.
- IL16 promotes Th1 and CD8+T cell migration, and its blockade reduces T cell movement, suggesting therapeutic potential.

## Abstract

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.

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 forty 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. 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. Graphical abstract created in BioRender. Wangriatisak, K. (2025) https://www.biorender.com/foa59mw

Graphical Abstract