Fig. 1. Inflammatory cascade and strategies for modulating inflammation.

a | Neutrophil recruitment and functions in inflammation. Neutrophils slowly roll along the endothelium by expressing P-selectin glycoprotein ligand 1 (PSGL1) and L-selectin, which bind to their corresponding ligands on the endothelium. Once at the site of inflammation, lymphocyte function-associated antigen 1 (LFA1) expressed on the neutrophil locks with intercellular adhesion molecule 1 (ICAM1) on the endothelium to initiate transmigration to the infected or inflamed tissue space. At the site of infection, neutrophils phagocytose pathogens or release reactive oxygen species (ROS), granules or neutrophil extracellular traps (NETs) to prevent pathogenic spread. Neutrophils then commit to apoptosis, initiating migration of other immune cell types. Monocytes and macrophages clean up dead cellular materials (pathogens and neutrophils) by efferocytosis and ultimately migrate to the liver and lymph nodes to remove and process pathogenic materials. Additionally, post efferocytosis monocytes shift to a pro-resolution phenotype to promote tissue restoration. b | Non-particle-based therapeutics for modulating inflammation. Stem cell therapies: transplanted mesenchymal stem cells (MSCs) can secrete immunosuppressive cytokines to promote regulatory T (T_reg) cell production and inhibit T helper 1 (T_H1) and T helper 2 (T_H2) cell differentiation or suppress immune cell recruitment and activation. Cytokines and antibody-based therapies: blocking antibodies or decoy receptors bind to inflammatory cytokines to inhibit their activity and dampen systemic inflammation. Vasculature blocking: biological agents prevent transmigration of immune cells by blocking specific leukocyte adhesion molecules on vascular endothelial cells, halting the inflammatory response. Targeted immune cell blocking: therapeutics can directly inhibit immune cells from pathological activation by blocking specific receptors on their surface. mAb, monoclonal antibody.