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Fig. 4 | Molecular Neurodegeneration

Fig. 4

From: Functional alterations of myeloid cells during the course of Alzheimer’s disease

Fig. 4

Stage-specific MDSC suppression of pro-inflammatory myeloid cells and T cell proliferation. Isolated patient MDSCs are co-cultured overnight (18 h) at 1:1 ratio with iPSC-generated M1 pro-inflammatory macrophages. a Production of IL-6 transcripts were highly suppressed by MDSCs from CDR0.5 patients while that suppression decreases as the patient advances to CDR1 and CDR2/3. (Control n = 10, CDR0.5 n = 11, CDR1 n = 10, and CDR2/3 n = 10). b Conditioned media from iPSC-M1 and patient MDSC co-cultures were analyzed via ELISA for changes in IL-6 protein. Changes in protein levels mirrored the IL-6 RNA suppression with CDR0.5 MDSCs causing a decrease in IL-6 protein production by M1 cells. These suppressive effects tapered off with advancing disease condition (Control n = 6, CDR0.5 n = 6, CDR1 n = 4, and CDR2/3 n = 5). c Addition of 5μg/mL neutralizing antibody for IL-10 reduces the IL-6 suppression in our MDSC: M1 assays. Numbers shown as averages ± SEM and statistics utilized were one-way ANOVA with Tukey post hoc (a, b) and student’s t-test (c). Isolated MDSCs were co-cultured with T responder cells at ratios of 1:1/4, 1:1/2, and 1:1 and stimulated for proliferation. d, e CDR0.5 MDSCs show hypersuppression of T cell proliferation compared with other groups. Late CDR2/3 MDSCs lost their T cell proliferation suppression below that of controls (Control n = 21, CDR0.5 n = 14, CDR1 n = 10, and CDR2/3 n = 10). f Arg1 expression in isolated MDSCs increase in CDR0.5 but decrease with increasing AD burden (Control n = 12, CDR0.5 n = 8, CDR1 n = 8, CDR2/3 n = 10). Numbers shown as averages ± SEM with one-way ANOVA with Tukey’s post hoc analysis. P-values are *p < 0.05, **p < 0.01, and ***p < 0.001

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