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...

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Main Authors: Anja Meyer, Joanna Schiller, David M Kofler, Ruth L Esser, Carolin Brück, Jan Thiele, Viktoria Golumba-Nagy, Eva Steinbach-Knödgen, Shuaifeng Yan, Carola tho Pesch, David Stahl
Format: Article
Language:English
Published: BMJ Publishing Group 2022-07-01
Series:Lupus Science and Medicine
Online Access:https://lupus.bmj.com/content/9/1/e000742.full
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author Anja Meyer
Joanna Schiller
David M Kofler
Ruth L Esser
Carolin Brück
Jan Thiele
Viktoria Golumba-Nagy
Eva Steinbach-Knödgen
Shuaifeng Yan
Carola tho Pesch
David Stahl
author_facet Anja Meyer
Joanna Schiller
David M Kofler
Ruth L Esser
Carolin Brück
Jan Thiele
Viktoria Golumba-Nagy
Eva Steinbach-Knödgen
Shuaifeng Yan
Carola tho Pesch
David Stahl
author_sort Anja Meyer
collection DOAJ
description 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.
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spelling doaj.art-6360ca39f1754987b5eaad4c50abe7cf2023-07-14T16:00:07ZengBMJ Publishing GroupLupus Science and Medicine2053-87902022-07-019110.1136/lupus-2022-000742Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLEAnja Meyer0Joanna Schiller1David M Kofler2Ruth L Esser3Carolin Brück4Jan Thiele5Viktoria Golumba-Nagy6Eva Steinbach-Knödgen7Shuaifeng Yan8Carola tho Pesch9David Stahl102 Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USADepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyDepartment I of Internal Medicine, University Hospital Cologne, Cologne, GermanyObjective 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.https://lupus.bmj.com/content/9/1/e000742.full
spellingShingle Anja Meyer
Joanna Schiller
David M Kofler
Ruth L Esser
Carolin Brück
Jan Thiele
Viktoria Golumba-Nagy
Eva Steinbach-Knödgen
Shuaifeng Yan
Carola tho Pesch
David Stahl
Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLE
Lupus Science and Medicine
title Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLE
title_full Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLE
title_fullStr Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLE
title_full_unstemmed Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLE
title_short Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4+ T-cell migration in SLE
title_sort truncated isoforms of gpsm2 containing the goloco motif region promote cd4 t cell migration in sle
url https://lupus.bmj.com/content/9/1/e000742.full
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