Sex-specific differences in ICOS+ T helper cell differentiation in systemic lupus erythematosus patients with low disease activity
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 oc...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
01 March 2024
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| In: |
Clinical and experimental medicine
Year: 2024, Jahrgang: 24, Pages: 1-13 |
| ISSN: | 1591-9528 |
| DOI: | 10.1007/s10238-024-01307-1 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s10238-024-01307-1
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| Verfasserangaben: | Lisa Wu, Florian Kälble, Hanns-Martin Lorenz, Martin Zeier, Matthias Schaier, Andrea Steinborn |
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| 245 | 1 | 0 | |a Sex-specific differences in ICOS+ T helper cell differentiation in systemic lupus erythematosus patients with low disease activity |c Lisa Wu, Florian Kälble, Hanns-Martin Lorenz, Martin Zeier, Matthias Schaier, Andrea Steinborn |
| 246 | 3 | 3 | |a Sex-specific differences in ICOS + T helper cell differentiation in systemic lupus erythematosus patients with low disease activity |
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| 520 | |a 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. | ||
| 650 | 4 | |a Inducible costimulatory molecule (ICOS) | |
| 650 | 4 | |a Recent thymic emigrants (RTEs) | |
| 650 | 4 | |a Responder T cells (Tresps) | |
| 650 | 4 | |a Resting mature naïve cells (MNs) | |
| 650 | 4 | |a Sex-specific CD4+ T cell differentiation | |
| 650 | 4 | |a Systemic lupus erythematosus (SLE) | |
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