Interferon-α activates interleukin-1 receptor-associated kinase 1 to induce regulatory T-cell apoptosis in patients with systemic lupus erythematosus

作者：Li, Mingfang; Yu, Datang; Wang, Yu; Luo, Na; Han, Guangming^*; Yang, Bin^*

来源：JOURNAL OF DERMATOLOGY, 2021, 48(8): 1172-1185.

DOI：10.1111/1346-8138.15899

• apoptosis
• interferon&#8208
• &#945
• interleukin&#8208
• 1 receptor&#8208
• associated kinase 1
• regulatory T cells
• systemic lupus erythematosus

Impaired regulatory T-cell (Treg) responses and upregulated interleukin-1 receptor-associated kinase 1 (IRAK1) expression are associated with the development of human systemic lupus erythematosus (SLE). Here, we show that the levels of upregulated IRAK1 expression in circulating Tregs are correlated with the percentages of apoptotic Tregs, Systemic Lupus Erythematosus Disease Activity Index scores, and serum complement C3 levels in SLE patients. High levels of plasma interferon (IFN)-alpha in SLE patients induced IRAK1 phosphorylation to trigger Treg apoptosis, which was mitigated by IRAK1 inhibitor (IRAK-Inh) treatment. Bioinformatics indicated that IRAK1 activation was related to the IFN-alpha/beta and mitogen-activated protein kinase (MAPK) signaling in Tregs and IFN-alpha treatment induced the p38 and MAPK/ERK kinase 3/6 phosphorylation, which was attenuated by IRAK-Inh in Tregs. Treatment with IRAK-Inh effectively alleviated renal injury and promoted the survival of lupus-prone B6.MRL-Fas(lpr)/Nju mice. Therefore, IFN-alpha induced IRAK1 activation to promote Treg apoptosis, contributing to the pathogenesis of SLE and IFN-alpha/IRAK1 may be therapeutic targets for SLE.

• 单位
  南方医科大学