Erucic acid improves the progress of pregnancy complicated with systemic lupus erythematosus by inhibiting the effector function of CD8+ T cells

Yanling Chang; Meng Jiang; You Wang; Qiong Fu; Sihan Lin; Jiayue Wu; Wen Di

doi:10.1002/mco2.382

Erucic acid improves the progress of pregnancy complicated with systemic lupus erythematosus by inhibiting the effector function of CD8⁺ T cells

MedComm (2020). 2023 Sep 26;4(5):e382. doi: 10.1002/mco2.382. eCollection 2023 Oct.

Authors

Yanling Chang^{1

2}, Meng Jiang^{1

2}, You Wang^{1

2}, Qiong Fu^{3

4}, Sihan Lin^{1

2}, Jiayue Wu^{1

2}, Wen Di^{1

2

5}

Affiliations

¹ Department of Obstetrics and Gynecology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China.
² Department of Obstetrics and Gynecology Shanghai Key Laboratory of Gynecologic Oncology Shanghai China.
³ Department of Rheumatology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China.
⁴ Shanghai Institute of Rheumatology Shanghai China.
⁵ Department of Obstetrics and Gynecology, State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China.

Abstract

Pathogenic CD8⁺ T cells are pivotal contributors to the onset of systemic lupus erythematosus (SLE). Erucic acid (EA) has been proven to have anti-inflammatory activity. However, the capacity of EA to regulate pathogenic CD8⁺ T cells in the context of pregnancy complicated with SLE (pSLE) remains unclear. In our investigation, we observed augmented CD8⁺ T cell effector function juxtaposed with diminished EA levels in pSLE patients relative to healthy pregnant controls. Significantly, plasma EA levels exhibited a negative correlation with the severity of pSLE-associated complications. In blood from patients with pSLE, EA inhibited the effector function of CD8⁺ T cells, concurrently dampening the maintenance of stem cell-like memory CD8⁺ T cells. Mechanistically, EA orchestrated the inhibition of CD8⁺ T cell effector function by impeding signal transducer and activator of transcription 3 phosphorylation and promoting ferroptosis. Moreover, EA supplementation in pregnant MRL/lpr mice manifested as the attenuation of uterine CD8⁺ T cell effector function, culminating in the mitigation of placental pathological damage. Our findings uncover the immune response modulatory effects of EA upon pathogenic CD8⁺ cells, thereby unveiling new perspectives for therapeutic strategies targeting pSLE patients.

Keywords: CD8+ T cells; erucic acid; pregnancy; systemic lupus erythematosus.