Systemic Lupus Erythematosus Favors the Generation of IL-17 Producing Double Negative T Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jun 7

PMID 32503973

Citations 47

Authors

Hao Li

Iannis E Adamopoulos

Vaishali R Moulton

Isaac E Stillman

Zach Herbert

James J Moon

Amir Sharabi

Suzanne Krishfield

Maria G Tsokos

George C Tsokos

Affiliations

Soon will be listed here.

Abstract

Mature double negative (DN) T cells are a population of αβ T cells that lack CD4 and CD8 coreceptors and contribute to systemic lupus erythematosus (SLE). The splenic marginal zone macrophages (MZMs) are important for establishing immune tolerance, and loss of their number or function contributes to the progression of SLE. Here we show that loss of MZMs impairs the tolerogenic clearance of apoptotic cells and alters the serum cytokine profile, which in turn provokes the generation of DN T cells from self-reactive CD8 T cells. Increased Ki67 expression, narrowed TCR V-beta repertoire usage and diluted T-cell receptor excision circles confirm that DN T cells from lupus-prone mice and patients with SLE undergo clonal proliferation and expansion in a self-antigen dependent manner, which supports the shared mechanisms for their generation. Collectively, our results provide a link between the loss of MZMs and the expansion of DN T cells, and indicate possible strategies to prevent the development of SLE.

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