A Variant of sNASP Exacerbates Lymphocyte Subset Disorder and Nephritis in a Spontaneous Lupus Model Sle1.Yaa Mouse

Abstract

A variant of somatic nuclear autoantigenic sperm protein (sNASP) was identified from the murine lupus susceptibility locus Sle2c1 by whole exome sequencing (WES). Previous studies have shown that mutant sNASP could synergize with the Faslpr mutation in exacerbating autoimmunity and aggravating end-organ inflammation. In the current study, the sNASP mutation was introduced into Sle1.Yaa mice to detect whether it has a synergistic effect with Sle1 or Yaa loci. As expected, compared with Sle1.Yaa mice, Sle1.Yaa.ΔsNASP mice showed enlarged lymph nodes, aggravated renal inflammation, and shortened survival time. The proportions of CD3+ T cells, activated CD19+CD86+ B cells, Th1 cells in the spleen and lymph nodes, and Th17 cells in lymph nodes in Sle1.Yaa.ΔsNASP mice were increased compared to those in Sle1.Yaa mice. The levels of IFN-γ and TNF-α in the serum of Sle1.Yaa.ΔsNASP mice were higher than those of Sle1.Yaa mice. The above results show that mutant sNASP can interact with different lupus susceptibility genes and promote the disease process of systemic lupus erythematosus.

sNASP Mutation Aggravates to the TLR4-Mediated Inflammation in SLE by TAK1 Pathway

“…In comparison to the control B6.lpr mice, the B6.∆sNASP.lpr mice exhibited enlarged spleen and lymph nodes, elevated total counts of T and B cells, increased activation and effector T cells, heightened levels of autoantibodies, and significantly enhanced inflammation in the kidneys and lungs [ 6 ]. Furthermore, we introduced the sNASP mutation into Sle1.Yaa mice, which demonstrated higher proportions of CD3 + T cells and activated CD19 + CD86 + B cells in the spleen and lymph nodes compared to Sle1.Yaa mice [ 7 ].…”