Journal Article

Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells

Zhao, Tian X., Stewart, Andrew P., Waldron-Lynch, Frank, Todd, John A., Inaba, Akimichi, Tuong, Zewen Kelvin, Truman, Lucy, Wicker, Linda, Mathews, Rebeccah, Kennet, Jane, Saeb-Parsy, Kourosh, Sriranjan, Rouchelle, Clatworthy, Menna R., Mallat, Ziad, Cheriyan, Joseph

2023

Overview

Dysfunction of interleukin-10 producing regulatory B cells has been associated with the pathogenesis of autoimmune diseases, but whether regulatory B cells can be therapeutically induced in humans is currently unknown. Here we demonstrate that a subset of activated B cells expresses CD25, and the addition of low-dose recombinant IL-2 to in vitro stimulated peripheral blood and splenic human B cells augments IL-10 secretion. Administration of low dose IL-2, aldesleukin, to patients increases IL-10-producing B cells. Single-cell RNA sequencing of circulating immune cells isolated from low dose IL2-treated patients reveals an increase in plasmablast and plasma cell populations that are enriched for a regulatory B cell gene signature. The transcriptional repressor BACH2 is significantly down-regulated in plasma cells from IL-2-treated patients, BACH2 binds to the IL-10 gene promoter, and Bach2 depletion or genetic deficiency increases B cell IL-10, implicating BACH2 suppression as an important mechanism by which IL-2 may promote an immunoregulatory phenotype in B cells. The dysfunction of IL-10 secreting regulatory B cells has been linked to the pathogenesis of autoimmune disease. Here the authors show that low dose IL-2 therapy can enhance IL-10 production in regulatory B cell populations via the modulation of BACH2.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/21 / 13/31 / 13/51 / 38 / 38/91 / 631/250/127/1213 / 631/250/1619/40/1742 / 631/250/251/1574 / 631/250/2520 / 631/250/38 / Autoimmune diseases / B-Lymphocytes / Basic-Leucine Zipper Transcription Factors - genetics / Basic-Leucine Zipper Transcription Factors - metabolism / CD25 antigen / Depletion / Gene sequencing / Humanities and Social Sciences / Humans / Immune system / Immunoregulation / Interleukin 10 / Interleukin 2 / Interleukin-10 - metabolism / Interleukin-2 - adverse effects / Lymphocytes B / multidisciplinary / Pathogenesis / Peripheral blood / Phenotypes / Plasma Cells / Populations / Science / Science (multidisciplinary)