Figure 1. IRF5 is hyperactivated in immune cells from patients with SLE and in NZB/W F1 lupus-prone mice.

IRF5 activation was assessed by nuclear localization in CD45⁺CD14⁺ monocytes (Mo) (A) and CD45⁺CD19⁺ B cells (B) from healthy donors and patients with SLE in the New Jersey cohort using imaging flow cytometry. Data represent the percentage of IRF5 nuclear translocation; circles represent independent donors. (C and D) IRF5 localization determined in monocytes (C) and B cells (D) from healthy donors and patients with SLE in the New York cohort with clinically inactive (score = 0/1) or active (score = 2/3) disease. (E and F) Percentage of IRF5 nuclear translocation in monocytes and B cells from patients with SLE stratified by SLEDAI (E) and dsDNA antibody titers (F). (G–K) Correlation between the percentage of IRF5 translocation in B cells or monocytes and dsDNA titers (G and H) or serum IFN-α levels (J and K) by linear regression analysis. (L and M) IRF5 nuclear translocation in CD11b⁺ monocytes from cohort 1 (L) and cohort 2 (M) consisting of aging female NZB/W F1 and BALB/c mice. Black circles, NZB/W F1 mice; white circles, BALB/c. n = 3 mice/group/cohort. (N) Inhibition of IRF5 activation (10–21 weeks old) by N5-1 in CD11b⁺ monocytes. (O and P) Same as in L and M, except in B220⁺ B cells from cohort 1 (O) and cohort 2 (P). (Q) Same as in N, except inhibition of IRF5 activation is shown in B220⁺ B cells. (R and S) IRF5 translocation in CD3⁺CD4⁺ T cells (R) and CD3⁺CD8⁺ T cells (S) from aging female NZB/W F1 and BALB/c mice. n = 6 mice/group. Data represent the mean ± SEM. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001, by 2-way ANOVA with Bonferroni’s post hoc test.