RelB regulates the homeostatic proliferation but not the function of Tregs

Shuping Zhou,Wei Lin,Mingzhao Zhu,Zhaoxia Wang,Xiaofan Li,Qinghong Su,Weiwei Wu,Weidong Zhang,Zhaopeng Wang,Yong Yu

doi:10.1186/s12865-020-00366-9

Abstract

BackgroundRelB, a member of the NF-κB family, plays a critical role in the development of T cells. However, the role of RelB in Foxp3+ regulatory T cells (Tregs) remains controversial.ResultsUsing a bone marrow chimeric mouse model, we demonstrated that the expansion of Foxp3+ Tregs in vivo could be mediated by extrinsic mechanisms. RelB plays an important role in inhibiting the homeostatic proliferation of Tregs, but not their survival. Even with the heightened expansion, RelB−/− Treg cells displayed normal suppressive function in vitro. Among the expanded populations of Treg cells, most were nTreg cells; however, the population of iTregs did not increase. Mechanistically, RelB seems to regulate Treg proliferation independently of the signal transducer and activator of transcription 5 (STAT5) pathway.ConclusionsThese data suggest that RelB regulates Treg proliferation independently of the STAT5 pathway, but does not alter the function of Tregs. Further studies are warranted to uncover such mechanisms.

Highlights

RelB, a member of the NF-κB family, plays a critical role in the development of T cells
Regulatory T cells (Treg) cells To study the role of RelB on the regulation of Tregs, we first measured the percentage of Treg cells in the thymus and spleens of RelB−/− mice
Excluding the effect of stromal cells and epithelial cells on Tregs, RelB deficiency enhanced the proportion of Treg cells in the spleen and thymus

Summary

Introduction

RelB, a member of the NF-κB family, plays a critical role in the development of T cells. The role of RelB in Foxp3+ regulatory T cells (Tregs) remains controversial. RelB plays an important role in inhibiting the homeostatic proliferation of Tregs, but not their survival. Appropriate Treg homeostasis at the periphery plays a crucial role in the maintenance of selftolerance. Disturbances in this balance are frequently associated with autoimmune diseases. The role of RelB in the development of Foxp3+ regulatory T cells (Tregs) remains controversial. Other studies reported normal T cell development in RelB−/− mice [15, 16].

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