Abstract
This review summarizes the available evidence on hyaluronic acid's (HA's) role in immune response. HA is one of many components in the extracellular matrix that transmits signals from the extracellular microenvironment to cellular effector systems in immune cells. The final effect of these interactions depends on the type of cells and receptors used and the size of HA particles. HA's activation of intracellular signaling pathways leads to an immune response involving the release of pro- or anti-inflammatory cytokines and chemokines. These play a crucial role in defense mechanisms, such as protecting against pathogens and tissue healing after injuries. HA, as a signaling particle, is also involved in the intensification of the cytokine storm during COVID-19. Multifold increases in HA content in the lungs and the strength of its impact on the immune system define an "HA storm". The molecular mechanisms involved in inflammation and initiation, including the promotion of cancer, also begin in the microenvironment, and hyaluronic acid is a key element. In this paper, we focus on intra- and intercellular signaling pathways using HA participation rather than injection preparation based on HA use for esthetic treatment.