Baicalin ameliorates lupus autoimmunity by inhibiting differentiation of Tfh cells and inducing expansion of Tfr cells

Ji Yang,Xue Yang,Jie Yang,Ming Li

doi:10.1038/s41419-019-1315-9

Ji Yang, Xue Yang + Show 2 more

Open Access

https://doi.org/10.1038/s41419-019-1315-9

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Abstract

Baicalin is a natural compound isolated from Chinese herb, which has been reported as an anti-inflammatory drug. Here, we demonstrated that Baicalin treatment could reduce urine protein, inhibit anti-ds-DNA antibody titers, and ameliorate lupus nephritis in MRL/lpr lupus-prone mice. Baicalin inhibited Tfh cell differentiation and IL-21 production, but promoted Foxp3+ regulatory T cell differentiation including part of follicular regulatory T (Tfr) cells. Intravenous injection of Baicalin-induced Foxp3+ regulatory T cells could relieve nephritis, inhibit Tfh cell differentiation and IL-21 production. Baicalin inhibited mTOR activation, reduced mTOR agonist-mediated Tfh cell expansion and increased Tfr cells. These data suggest that Baicalin attenuates lupus autoimmunity by up- and downregulating the differentiation of Tfr cells and Tfh cells, respectively. Baicalin and ex vivo expanded Foxp3+ regulatory T cells are promising therapeutics for the treatment of lupus.

Highlights

Systemic lupus erythematosus (SLE) is a common autoimmune disease that involves multiple organ systems
We showed that treatment with Baicalin for 4 weeks reduced 24-h urine protein levels, relieved kidney inflammation, and inhibited serum anti-ds-DNA antibody production and kidney IgG deposition in MRL/lpr mice
These data indicate that Baicalin is an effective and promising drug for the treatment of lupus autoimmunity, which is consistent with our previous findings[26]

Summary

Introduction

Systemic lupus erythematosus (SLE) is a common autoimmune disease that involves multiple organ systems. The prevalence ranges from 20–150 cases in a population of 100,000 and appears to be increasing because the disease cannot be effectively cured[1]. Drugs such as glucocorticoids and immunosuppressive agents are used to treat SLE, but long-term use can lead to a range of side effects, it is urgent and necessary to find more safe and effective treatments for SLE. Circulating Tfh cells are increased in the blood of SLE patients and correlate with SLE severity, and increased numbers of Tfh cells lead to increased IL-21 production in lupus-prone mice[8,9,10,11,12,13,14,15].

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