Resolvin D1 inhibits T follicular helper cell expansion in systemic lupus erythematosus

Abstract

Objective

Resolvin D1 (RvD1) is one of the specialized pro-resolving lipid mediators, which control inflammation resolution and regulate immune responses. Previous research showed that RvD1 could block the progression of systemic lupus erythematosus (SLE). However, the detailed mechanism remains to be fully understood.

Method

Plasma RvD1 levels, and proportions of T follicular helper cells (Tfh cells) were measured in SLE patients and healthy controls. Plasma RvD1 levels and proportions of Tfh cells were quantitated in an MRL/lpr mouse model of lupus treated with RvD1. Naïve CD4⁺ T cells were purified from MRL/lpr mice to study the effect of RvD1 on Tfh cell differentiation in vitro.

Results

In patients, there were significant negative correlations between plasma RvD1 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, as well as between plasma RvD1 and anti-double-stranded DNA antibody levels, and numbers of peripheral Tfh cells and plasma cells. In MRL/lpr mice, the expected amelioration of disease phenotype and inflammatory response with RvD1 treatment correlated with decreased percentages of Tfh cells and plasma cells. In addition, the differentiation and proliferation of Tfh cells were markedly suppressed by RvD1 in vitro.

Conclusion

RvD1 may control SLE progression through the suppression of Tfh cell differentiation and subsequent inhibition of B-cell responses.

Acknowledgements

We are grateful to the volunteers who participated in this study. We are also grateful to Robert A Eisenberg, Department of Rheumatology, University of Pennsylvania, for writing assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

LH and JW participated in study design, data collection, data analysis, data interpretation, and drafting the paper. JC and XS participated in patient recruitment, animal experiments, and data collection. TC and MW supervised the whole research, designed the study, interpreted the data, and wrote the paper. All authors contributed to the article and approved the submitted version.

Data availability statement

The data sets used during the current study are available from the corresponding author upon reasonable request.

Ethics statement

The study involving human participants was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Soochow University, The patients/participants provided their written informed consent to participate in this study. The animal study was reviewed and approved by the Committee of Experimental Animal Administration of Soochow University.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/03009742.2024.2344906

Additional information

Funding

This research was funded by the National Natural Science Foundation of China [grant number 82101887] and the Horizontal Scientific Research Project of Soochow University [grant numbers P112200318 and P112202223], to Mingjun Wang and Tao Cheng.