Impaired Differentiation of Highly Proliferative ICOS-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Sep 10

PMID 34502409

Citations 4

Authors

Florian Kalble

Lisa Wu

Hanns-Martin Lorenz

Martin Zeier

Matthias Schaier

Andrea Steinborn

Affiliations

Soon will be listed here.

Abstract

Dysregulations in the differentiation of CD4-regulatory-T-cells (Tregs) and CD4-responder-T-cells (Tresps) are involved in the development of active systemic lupus erythematosus (SLE). Three differentiation pathways of highly proliferative inducible costimulatory molecule (ICOS)- and less proliferative ICOS-CD45RACD31-recent-thymic-emigrant (RTE)-Tregs/Tresps via CD45RACD31-memory-Tregs/Tresps (CD31-memory-Tregs/Tresps), their direct proliferation via CD45RACD31-mature naïve (MN)-Tregs/Tresps, and the production and differentiation of resting MN-Tregs/Tresp into CD45RACD31-memory-Tregs/Tresps (CD31-memory-Tregs/Tresps) were examined in 115 healthy controls, 96 SLE remission patients, and 20 active disease patients using six color flow cytometric analysis. In healthy controls an appropriate sequence of these pathways ensured regular age-dependent differentiation. In SLE patients, an age-independently exaggerated differentiation was observed for all Treg/Tresp subsets, where the increased conversion of resting MN-Tregs/Tresps particularly guaranteed the significantly increased ratios of ICOS-Tregs/ICOS-Tresps and ICOS-Tregs/ICOS-Tresps during remission. Changes in the differentiation of resting ICOS-MN-Tresps and ICOS-MN-Tregs from conversion to proliferation caused a significant shift in the ratio of ICOS-Tregs/ICOS-Tresps in favor of ICOS-Tresps and a further increase in the ratio of ICOS-Tregs/ICOS-Tresps with active disease. The differentiation of ICOS-RTE-Tregs/Tresps seems to be crucial for keeping patients in remission, where their limited production of proliferating resting MN-Tregs may be responsible for the occurrence of active disease flares.

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