p16INK4a-deficient macrophages phenotypically and functionally resemble IL-4–polarized alternatively activated macrophages. Protein secretion of IL-6 (A), TNF (B), and IL-1Rn (C) was measured in the culture medium of p16+/+ and p16−/− BMDM by ELISA. (D-F) QPCR analysis of Arg-I (D), Ym1/2 (E), and Mgl2 (F) of p16+/+ and p16−/− AAMφ polarized by addition of 15 ng/mL IL-4 from day 0 of differentiation. (G) Schematic representation of the indirect coculture experiment. (H-I) LPS-induced secretion of IL-6 (H), and TNF (I) was determined by ELISA in p16+/+ BMDM supernatants resulting from indirect coculture. Statistically significant differences are indicated (t test; ***P < .001, **P < .01, and *P < .05).