Phosphodiesterase 1b (Pde1b) governs development and immune responses of myeloid and lymphoid cells through regulation of cyclic nucleotide-dependent protein kinases

This study demonstrates that selective expression of the calcium/calmodulin-dependent phosphodiesterase 1b (Pde1b) in specific dendritic cell (DC) and macrophage subsets is essential for promoting inflammation and adaptive immunity.

Utilizing single-cell RNA sequencing and multiparameter flow cytometry, Pde1b deficiency was found to alter gene expression and protein functions involved in development or immune effector activity in DC, macrophages, granulocytes, B cells, NK cells and memory T cells. In vivo pathogen challenge studies in Pde1b-deficient mice resulted in markedly attenuated pro-inflammatory and antigen-specific T cell responses. Notably, Pde1b-deficient DC and macrophages exhibited elevated cyclic nucleotides levels and enhanced cyclic nucleotide-dependent PKA and PKG activity.