Background Transcolbalamin2 (TCN2) is a vitamin B12 transport plasma protein that facilitates cellular uptake of cobalamin. TCN2 deficiency displays a metabolic disorder with immunodeficiency disease. However, its functions in autoimmunity diseases remain unknown. We attempt to investigate the effects of TCN2 on immune cells in systemic lupus erythema (SLE).
Methods TCN2 expression change in SLE was detected by analyzing our RNA-seq data and microarray from the GEO database and further examined by qPCR. TCN2-KO mice were developed and induced to lupus via pristane injection. The anti-dsDNA and urine protein level, skin, and renal involvement were assessed by ELISA, urine-protein test strips, hematoxylin-eosin (HE), PAS, and immunofluorescent staining. The frequency of immune cells in blood and kidney was investigated via flow cytometry.
Results We identified increased TCN2 expression in the blood and kidneys of SLE and confirmed upregulated expression of TCN2 in CD19+ B cells and CD4+ T cells in lupus patients and lupus-like mice compared to healthy controls. Then we successfully knocked out TCN2 in C57B/L6. Further studies demonstrated that downregulated expression of TCN2 ameliorated lupus symptoms, which displayed lower dsDNA levels, miler urine protein, and less mesangial hypercellularity and IgG deposition in the glomerulus. Flow cytometry results showed that inhibition of TCN2 remarkably reduced the frequency of B cells and CXCR5+ ICOS+ Tfh cells in the spleen and kidney of lupus-like mice.
Conclusions These results substantiate the involvement of TCN2 in SLE development. Inhibition of TCN2 overexpression alleviated renal injury by reducing Tfh and B cell infiltration. Our findings imply that cobalamin metabolism might be associated with aberrant germinal center responses and provide a novel target for SLE treatment.
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