Erschienen:
Springer Science and Business Media LLC, 2022
Erschienen in:
Arthritis Research & Therapy, 24 (2022) 1
Sprache:
Englisch
DOI:
10.1186/s13075-022-02769-y
ISSN:
1478-6362
Entstehung:
Hochschulschrift:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Interleukin-2 (IL-2) and the high-affinity IL-2 receptor (IL-2R) are essential for the survival of regulatory T cells (Tregs) which are the main players in immune tolerance and prevention of autoimmune diseases. Sjögren’s syndrome (SS) is a chronic autoimmune disease predominantly affecting women and is characterised by sicca symptoms including oral and ocular dryness. The aim of this study was to investigate an association between IL-2R and Treg function in patients with SS of different severity defined by the salivary flow rate.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In a cross-sectional study, we determined plasma soluble IL-2R (sIL-2R) levels in women with SS (<jats:italic>n</jats:italic>=97) and healthy females (<jats:italic>n</jats:italic>=50) using ELISA. A subset of those (<jats:italic>n</jats:italic>=51) was screened for Treg function measured by the STAT5 signalling response to IL-2 using phospho-flow cytometry.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that elevated plasma levels of sIL-2R were positively associated with the severity of SS reflected by a pathologically low salivary flow. Phospho-flow analysis revealed that patients with SS have a significantly lower frequency of pSTAT5<jats:sup>+</jats:sup>Tregs upon IL-2 stimulation compared with healthy individuals, while the frequency of Tregs and pSTAT5 in conventional T cells remained unchanged. In addition, we observed more pSTAT5<jats:sup>+</jats:sup>Tregs at baseline in patients with SS, which is significantly associated with seropositivity and elevated sIL-2R.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our data indicates that Tregs have a weakened immunosuppressive function in patients with SS due to impaired IL-2/IL-2R signalling capacity. This could mediate lymphocytic infiltration into salivary glands inducing sicca symptoms. We believe that sIL-2R could act as a useful indicator for SS and disease severity.</jats:p></jats:sec>