Figure 18: Proposed β2-AR signaling pathways responsible for differential receptor regulation of IFN-γ production in immune cells from different secondary lymphoid organs in adjuvant-induced arthritis. A) In the DLN, where a β2-AR agonist increased IFN-γ production, receptor phosphorylation patterns support phosphorylation of the receptor by PKA and GRK5/6. This phosphorylation pattern induces receptor uncoupling from Gs and recruitment of β-arrestin-2 to the receptor, which shifts signaling towards the ERK1/2 pathway. This shift in receptor signaling then promotes IFN-γ production. B) In spleen cells, the inability of a β-AR agonist to induce an increase in cAMP coupled with the pattern of receptor phosphorylation we observed is consistent with phosphorylation by PKA and GRK2. GRK2 phosphorylation uncouples the receptor from Gs and recruits β-arrestin 1 resulting in receptor desensitization. C. In contrast, MLN cell the ability of the β2-AR agonist to suppress IFN-γ production in AA rats indicates receptors in these cells signal through the classical cAMP-PKA pathway.