The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE

Annals of the Rheumatic Diseases
Niklas HagbergLars Rönnblom

Abstract

Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs. In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resul...Continue Reading

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Citations

Nov 22, 2018·Expert Opinion on Investigational Drugs·Chi Chiu Mok
Dec 12, 2018·Annals of the Rheumatic Diseases·Yukinori OkadaKazuhiko Yamamoto
Nov 26, 2019·European Journal of Immunology·Hideki Ueno
Nov 28, 2019·Autoimmunity·Farhana Muhammad YusoffNorhanani Mohd Redzwan
Jun 18, 2019·Lupus Science & Medicine·Mary K Crow, Lars Ronnblom
Sep 10, 2019·Lupus Science & Medicine·Lars Rönnblom, Dag Leonard
May 20, 2020·Scandinavian Journal of Immunology·Niklas HagbergLars Rönnblom
Jun 20, 2020·Clinical Reviews in Allergy & Immunology·Jiao JiangQianjin Lu
Mar 20, 2019·Annals of Human Genetics·Bianca BiancoCaio P Barbosa
May 7, 2020·Rheumatology·Jenna L ThomasonAnd Grant Hughes
Jun 12, 2018·Current Opinion in Rheumatology·Gudny Ella ThorlaciusLars Rönnblom
Dec 5, 2020·Biomedicines·Ludmiła Szewczak, Katarzyna Donskow-Łysoniewska
Nov 28, 2020·Current Opinion in Immunology·Mariana PostalTimothy B Niewold
Apr 16, 2021·Frontiers in Cellular and Infection Microbiology·Zhangchun GuanGuang Yang
Jul 4, 2021·Rheumatic Diseases Clinics of North America·Jacqueline L ParedesTimothy B Niewold
Sep 2, 2021·Expert Review of Clinical Immunology·Shingo Nakayamada, Yoshiya Tanaka
Aug 30, 2021·Lancet·Donal P McLornanClaire N Harrison
Oct 13, 2021·Science Signaling·Michiel van der VlistLinde Meyaard

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Methods Mentioned

BETA
density-gradient centrifugation
ELISA
flow cytometry
PMA

Software Mentioned

GraphPad Prism
SPSS Statistics
Tree Star
FlowJo
FACSDiva

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