p16^INK4a deficiency induces a gene expression profile resembling IL-4–induced macrophage polarization. Microarray analysis using mRNA from p16^−/− BMDM compared with p16^+/+ BMDM showed (A) decreased mRNA expression of classically activated macrophage-associated genes and (B) increased mRNA expression of alternatively activated macrophage-associated genes. Data are expressed as fold change relative to p16^+/+ BMDM. (C) Differential gene expression in p16^−/− BMDM relative to p16^+/+ BMDM was correlated with the changes induced in IL-4–induced p16^+/+ AAMφ. The figure shows 2 log values of the probesets significantly (P < .05) regulated only in p16^−/− BMDM (red dots), only in IL-4–polarized p16^+/+ AAMφ (green dots) and by both conditions (blue dots), compared with p16^+/+ BMDM. The x-axis represents differences in gene expression induced by IL-4, whereas the y-axis represents the effect of p16^INKa deficiency. These comparisons are depicted in the schematic representation of the protocol in the corresponding colors. Pearson correlation analysis was done for probesets differentially expressed by both conditions (blue). (D) Heat map of p16^+/+ BMDM, p16^−/− BMDM, IL-4–polarized p16^+/+, and p16^−/− AAMφ gene expression profiles. Colors fluctuate from blue (poorly expressed) to green (intermediate expression) and yellow (high expression). Additional information regarding gene description, fold induction, and P value can be found in supplemental Table 3.