Background/Purpose: Fractalkine (FKN, CX3CL1) and its receptor, CX3CR1, play an important role in chemotaxis of immune cells, such as cell adhesion, migration and infiltration into the organs. Several lines of evidence indicated that serum level of FKN was elevated and correlated with disease activity in patients with rheumatoid arthritis (RA) and the expression of CX3CR1 is upregulated especially in peripheral intermediate monocytes, CD14⁺⁺CD16⁺in RA patients as compared to healthy controls (HC). On the other hand, it has been reported that elevated expression CX3CR1⁺macrophages were infiltrated in the kidney of lupus patients and CD16⁺monocytes within the glomerular blood vessels of the patients corresponds to the high CX3CR1⁺expressing monocytes. In this study, we investigated the expression level of CX3CR1 in peripheral monocytes and T cells from patients with systemic lupus erythematosus (SLE) and HC to elucidate the possible involvement of CX3CR1 in immunological features of SLE.

Methods: The expression level of CX3CR1 in peripheral monocytes (classical monocytes: CD14⁺⁺CD16^–, intermediate monocytes: CD14⁺⁺CD16⁺, non-classical monocytes: CD14⁺CD16⁺⁺), CD4 and CD8 T cells was analyzed by FACS with whole blood samples from patients with SLE active (SLEDAI : >10, n = 22), inactive (SLEDAI: <4, n = 22) and HC (n = 34).Differences between the groups were examined for statistical significance using the t test for single comparisons. Correl correlation analysis was employed for evaluation of the linear relationship between two continuous variables.

Results: FACS analysis revealed that the proportion of CD14⁺⁺CD16⁺monocytes among CD14⁺ cells was significantly elevated in SLE active (p = 0.0017) and SLE inactive (p = 0.0002) patients as compared to HC, whereas no significant difference was observed in that proportion between SLE active and inactive patients. Notably, the proportion of CX3CR1 positive cells in CD14⁺⁺CD16⁺monocytes was significantly lower in SLE active patients than patients with SLE inactive (p = 0.014) and HC (p = 0.002), whereas that proportion was not significantly different between SLE inactive and HC. In addition, the proportion of CX3CR1 positive cells in CD4 and CD8 T cells was not significantly different among the groups.

Conclusion: These results give the possibility that FKN binds its receptor, CX3CR1, expressed on CD14⁺⁺CD16⁺monocytes in SLE, and the cells consequently migrate into the organs through peripheral blood. Our data suggest that targeting FKN signaling may be effective for suppressing inflammatory monocyte recruitment to the organs in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-expression-of-cx3cr1-in-peripheral-cd14cd16monocytes-is-a-novel-feature-of-patients-with-systemic-lupus-erythematosus/