Sex-specific differences in ICOS+ T helper cell differentiation in systemic lupus erythematosus patients with low disease activity

• Verfasst von: Wu, Lisa [VerfasserIn]
• Verfasst von: Kälble, Florian [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Zeier, Martin [VerfasserIn]
• Verfasst von: Schaier, Matthias [VerfasserIn]
• Verfasst von: Steinborn-Kröhl, Andrea [VerfasserIn]
• Titel: Sex-specific differences in ICOS+ T helper cell differentiation in systemic lupus erythematosus patients with low disease activity
• Verf.angabe: Lisa Wu, Florian Kälble, Hanns-Martin Lorenz, Martin Zeier, Matthias Schaier, Andrea Steinborn
• E-Jahr: 2024
• Jahr: 01 March 2024
• Umfang: 13 S.
• Illustrationen: Illustrationen
• Fussnoten: Online veröffentlicht: 01. März 2024 ; Gesehen am 11.07.2024 ; Im Titel ist das Pluszeichen hochgestellt
• Titel Quelle: Enthalten in: Clinical and experimental medicine
• Ort Quelle: Milano : Springer, 2001
• Jahr Quelle: 2024
• Band/Heft Quelle: 24(2024), Artikel-ID 47, Seite 1-13
• ISSN Quelle: 1591-9528
• DOI: doi:10.1007/s10238-024-01307-1
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Inducible costimulatory molecule (ICOS)
• Sach-SW: Recent thymic emigrants (RTEs)
• Sach-SW: Responder T cells (Tresps)
• Sach-SW: Resting mature naïve cells (MNs)
• Sach-SW: Sex-specific CD4+ T cell differentiation
• Sach-SW: Systemic lupus erythematosus (SLE)
• K10plus-PPN: 1895128285

Abstract

Systemic lupus erythematosus (SLE) is a sex biased chronic autoimmune disease affecting predominantly females during reproductive ages. Changes in the ratio of inducible costimulatory molecule (ICOS)+ regulatory (Treg) and non-regulatory responder (Tresp) CD4+ T cells proved to be crucial for the occurrence of high disease activity. Here, we investigated how the differentiation of ICOS+CD45RA+CD31+ recent thymic emigrant (RTE) Tresps into CD45RA−CD31− memory Tresps affects the percentages of ICOS+ Tresps within total CD4+ T cells. Three different pathways (pathway 1 via CD45RA−CD31+ memory Tresps, pathway 2 via direct proliferation and pathway 3 via resting mature naïve CD45RA+CD31− (MN) cells) were examined in healthy controls and SLE remission patients separated by sex. In female SLE remission patients, immunosuppressive therapy inhibited the ICOS+ RTE differentiation via CD45RA−CD31+ memory Tresps and direct proliferation, leaving an age-independently increased differentiation into CD45RA−CD31− memory Tresps by conversion of resting MN Tresps compared with healthy controls. Due to exhaustion of this pathway with age, no age-dependent change in the percentages of ICOS+ Tresps within total CD4+ T cells could be found. In contrast, no age-independently increased differentiation could be detected in men due to sufficient immunosuppression of all three pathways. This allowed an age-dependent differentiation of ICOS+ RTE Tresps into CD45RA−CD31− memory Tresps by conversion of resting MN Tresps, resulting in age-dependently increasing percentages of ICOS+ Tresps within total CD4+ T cells. We hypothesize that the sex-specific differential effect of immunosuppression on the differentiation of ICOS+ Tresps may explain the sex- and age-dependent occurrence of high disease activity.