Cytokines on the way to secretion
Paulina Kamińska, Aleksandra Tempes, Ela Scholz, Anna R. Malik
Abstract
The activation of immune cells by pro-inflammatory or immunosuppressive stimuli is followed by the secretion of immunoregulatory cytokines which serve as messengers to activate the immune response in target cells. Although the mechanisms that control the secretion of cytokines by immune cells are not yet fully understood, several key aspects of this process have recently emerged. This review focuses on cytokine release via exocytosis and highlights the routes of cytokine trafficking leading to constitutive and regulated secretion as well as the impact of sorting receptors on this process. We discuss the involvement of cytoskeletal rearrangements in vesicular transport, secretion, and formation of immunological synapses. Finally, we describe the non-classical pathways of cytokine release that are independent of vesicular ER-Golgi transport. Instead, these pathways are based on processing by inflammasome or autophagic mechanisms. Ultimately, understanding the molecular mechanisms behind cytokine release may help to identify potential therapeutic targets in diseases associated with altered immune responses. • Cytokine secretion employs several alternative mechanisms. • Constitutive secretion of cytokines often proceeds via recycling endosomes. • Cytoskeletal rearrangements are critical for the regulated secretion of cytokines. • Immunological synapses represent an important mechanism of cytokine release. • Sorting by the VPS10P domain receptors is involved in cytokine release.