KLRG1 is reduced on NK cells in SLE patients, inversely correlates with disease activity and is modulated by hydroxychloroquine in vitro

OBJECTIVES: Killer cell lectin-like receptor G 1 (KLRG1), a transmembrane receptor with inhibitory capacity expressed in human immune cells, emerged as a novel susceptibility gene for systemic lupus erythematosus (SLE). The aim of this study was to investigate the expression of KLRG1 in SLE patients compared to healthy controls (HC) on both NK and T cells and to evaluate its possible involvement in SLE pathogenesis.

METHODS: Eighteen SLE patients and twelve healthy controls were enrolled. Peripheral blood mononuclear cells (PBMCs) from these patients were phenotypically characterized by immunofluorescence and flow cytometry. The effect of the hydroxychloroquine (HCQ) in vitro on KLRG1 expression and its signaling mediated functions in NK cells were analyzed.

RESULTS: KLRG1 expression was significantly reduced on the analyzed immune cell populations in SLE patients compared to HC, especially on total NK cells. Moreover, expression of KLRG1 on total NK cells inversely correlated with the SLEDAI-2K. A direct association between KLRG1 expression on NK cells and patients' treatment with HCQ was observed. In vitro treatment with HCQ increased KLRG1 expression on NK cells. In HC, KLRG1+ NK cells showed reduced degranulation and IFNγ production, while in SLE patient, this inhibition occurred only for the IFNγ production.

CONCLUSION: With this study we revealed a reduced expression and an impaired function of KLRG1 on NK cells in SLE patients. These results suggest a possible role of KLRG1 in the pathogenesis of SLE and as a novel biomarker of this disease.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:32

Enthalten in:

Lupus - 32(2023), 4 vom: 22. Apr., Seite 549-559

Sprache:

Englisch

Beteiligte Personen:

Novelli, Lucia [VerfasserIn]
Barbati, Cristiana [VerfasserIn]
Capuano, Cristina [VerfasserIn]
Recalchi, Serena [VerfasserIn]
Ceccarelli, Fulvia [VerfasserIn]
Vomero, Marta [VerfasserIn]
Alessandri, Cristiano [VerfasserIn]
Morrone, Stefania [VerfasserIn]
Conti, Fabrizio [VerfasserIn]

Links:

Volltext

Themen:

4QWG6N8QKH
Autoimmunity
Biomarker
Hydroxychloroquine
Journal Article
KLRG1
KLRG1 protein, human
Lectins, C-Type
NK cells
Receptors, Immunologic
Systemic lupus erythematosus

Anmerkungen:

Date Completed 19.04.2023

Date Revised 19.04.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1177/09612033231160979

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM353823287