In skin disorders, the PDE4 inhibitor apremilast, reduces the activation of M1/M2 macrophages, T-cells, and fibroblast skin accumulation in various animal models of systemic sclerosis (SSc) (Lu et al. 2021; Maier et al. 2017) without direct effect on skin fibroblasts from SSc patients (Maier et al. 2017). Here, PDE4A is linked to systemic sclerosis.