Fig. 2: Rab4A expands CD4+ T cells at the expense of CD8+ T cells both in B6 and B6.TC mice. | Nature Communications

Fig. 2: Rab4A expands CD4+ T cells at the expense of CD8+ T cells both in B6 and B6.TC mice.

From: Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation

Fig. 2

A Expansion of T cells at the expense of B cells in the spleens B6.TC/Rab4AQ72L mice over B6/Rab4AQ72L controls in 20-week-old female mice. The numbers (n) of mice in each experimental group were as follows: B6 (n = 6), B6/Rab4AQ72L (n = 8), B6/Rab4AQ72L-KO (n = 5), B6.TC (n = 9), B6.TC/Rab4AQ72L (n = 8), B6.TC/Rab4AQ72L-KO (n = 8); CD3+ T cells 2-way ANOVA p = 0.5234; Sidak’s post-hoc test p values corrected for multiple comparisons: B6/Rab4AQ72L vs B6.TC/Rab4AQ72L p = 0.0537. CD19+ B cells 2-way ANOVA p = 0.9083; Sidak’s post-hoc test p values corrected for multiple comparisons: B6/Rab4AQ72L vs B6.TC/Rab4AQ72L p = 0.0349. CD3+ vs CD19+ B cells in B6/Rab4AQ72L vs B6.TC/Rab4AQ72L mice comparison by 2-way ANOVA p < 0.0001. B Rab4A activation elicits the expansion of CD4+ T cells at the expense of CD8+ T cells within the T-cell compartment in B6/Rab4AQ72L and B6.TC/Rab4AQ72L mice. Left panel, representative flow cytometry dot plots; right panel, cumulative analysis of abundance of CD4+ and CD8+ T cells. The numbers (n) of mice in each experimental group were as follows: B6 (n = 6), B6/Rab4AQ72L (n = 8), B6/Rab4AQ72L-KO (n = 5), B6.TC (n = 9), B6.TC/Rab4AQ72L (n = 8), B6.TC/Rab4AQ72L-KO (n = 8); C Accumulation of mitochondrial mass and elevation of the mitochondrial transmembrane potential (ΔΨm) in CD4+ T cells of B6/Rab4AQ72L and B6.TC/Rab4AQ72L mice and their reversal upon Rab4A deletion in B6/Rab4AQ72L-KO and B6.TC/Rab4AQ72L-KO mice. Relative to the mitochondrial mass, ΔΨm was elevated in CD4+ T cells of B6.TC/Rab4AQ72L mice, indicating mitochondrial hyperpolarization (MHP). The numbers (n) of mice in each experimental group were as follows: B6 (n = 2), B6/Rab4AQ72L (n = 2), B6/Rab4AQ72L-KO (n = 4), B6.TC (n = 4), B6.TC/Rab4AQ72L (n = 4), B6.TC/Rab4AQ72L-KO (n = 4); D MHP in CD8+ T cells of B6/Rab4AQ72L mice is reversed upon Rab4A deletion in B6/Rab4AQ72L-KO mice. The numbers (n) of mice in each experimental group were as follows: B6 (n = 2), B6/Rab4AQ72L (n = 2), B6/Rab4AQ72L-KO (n = 4), B6.TC (n = 4), B6.TC/Rab4AQ72L (n = 4), B6.TC/Rab4AQ72L-KO (n = 4); Dot plots represent individual mice matched for genotype, age, and sex within each experimental group and processed in parallel. 2-way ANOVA p values are displayed for multiple comparisons of Rab4 WT, Rab4AQ72L, and Rab4AQ72L-KO mice within B6 control and B6.TC SLE strains. Overall 2-way ANOVA p values are shown in the header of each figure panel, while Tukey’s post-hoc test p values < 0.05 over connecting bars reflect comparison between experimental groups.

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