Comparative transcriptome analysis reveals a potential role for CaMK4 in γδT17 cells from systemic lupus erythematosus patients with lupus nephritis

gamma delta T cells may be involved in the onset of systemic lupus erythematosus (SLE) though the production of pro-inflammatory cytokines. IL-17 has been shown to play an important role in the pathogenesis of SLE with lupus nephritis (LN). Although some investigations have indicated that gamma delta T cells are the major producing cells of IL-17 (gamma delta T17 cells), the function of gamma delta T17 cells in SLE with LN has not yet been fully established. In the present study, transcriptome sequencing analysis was performed to identify genes in gamma delta T cells differentially expressed between SLE patients with LN and healthy subjects. We first showed that IL-17A expression level in SLE patients is higher than in healthy controls, and the most pronounced increase occurred in the SLE patients with LN. The population of gamma delta T cells was shown to be smaller in SLE patients, but there was no difference between SLE patients and controls with respect to gamma delta T17 cells. Transcriptome sequencing analysis revealed 28 different genes associated with SLE disease among the gamma delta T cells from SLE patients with LN. In these genes, CaMK4 was further confirmed to be differently expressed in SLE patients. Finally, CaMK4 inhibitor was shown to inhibit the secretion of IL-17A in gamma delta T cells from SLE with LN. Our results suggest that CaMK4 may participate in the pathogenic mechanism of SLE with LN induced by gamma delta T17 T cells. This constitutes evidence that CaMK4 inhibitors may serve as effective reagents in the treatment of SLE with LN.