Background Lupus nephritis (LN) is one of the most common organ-specific injury of systemic lupus erythematosus (SLE) and has great influence on patients’ prognosis. Some research showed that interleukin (IL) -22 was enriched in the kidney tissue of MRL/lpr mice, and it was related to kidney lesions. The proportion of Th22 cells and IL-22 in periphery blood mononucleated cell (PBMC) and kidney tissue of LN patients were found increased, suggesting that IL-22/Th22 may be participated in the development of LN. About seventy-five percent of SLE patients showed significantly up-regulated of serum IFN-α (the main active component of IFN-I) and increased transcription of IFN-α-regulated genes in PBMC. Injected with IFN-α showed lupus phenotype increased in MRL/lpr mice.

Methods The effect of IFN-I on Th22 cell differentiation and the related key intracellular signaling pathway were investigated by in vitro cell experiments and in vivo animal model intervention, to explore whether IFN-I affects IL-22 production and Th22 differentiation.

Results Complement 3 levels were lower and SLEDAI-2K were higher in the LN group than in the non-LN group. Comparison of IL-22/IL-22R1 immunohistochemical (IHC) images in kidney between healthy control (HC) and LN patients, and the quantitative levels of IL-22/IL-22R1 in the LN group were quite higher than in the HC group. Similar results could be found in comparison between premortem (8 weeks) and postmortem (27 weeks) NZB/W F1 mice. Flow cytometry showed the high concentration of IFN-α could be inhibitor of the differentiation of Th22 cell.

Conclusions IL-22/Th22 could be participated in the development of LN, and IFN-I may play a significant role in activating the IL-22/Th22 pathway.