Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4(+) T-cell migration in SLE

OBJECTIVE: SLE is an autoimmune disease with a complex pathogenesis. T-cell infiltration into organs contributes to inflammation and organ damage in SLE. Recently, G-protein signalling modulator 2 (GPSM2) has been shown to be implicated in T-cell migration. METHODS: We analysed the expression levels of GPSM2 and of a truncated isoform of GPSM2 containing the GoLoco motif region in CD4(+) T cells from patients with SLE and from healthy individuals by western blot. In a next step, we studied the role of the truncated GPSM2 isoform using a CD4(+) T-cell migration assay. RESULTS: Our experiments revealed comparable levels of GPSM2 in CD4(+) T cells from patients with SLE and healthy controls. In contrast, the truncated 35 kDa isoform of GPSM2 was significantly more highly expressed in CD4(+) T cells from patients with SLE as compared with healthy subjects. Antibody-mediated blockade of the 35 kDa GPSM2 isoform reduced the in vitro capacity of CD4(+) T cells to migrate towards the chemokine CCL20. CONCLUSIONS: A truncated GPSM2 isoform containing the GoLoco motif region is upregulated in CD4(+) T cells from patients with SLE and promotes CD4(+) T-cell migration. Targeting this isoform with specific antibodies might be a promising approach to reduce CD4(+) T-cell infiltration into inflamed tissues and to prevent organ damage in SLE.