Immune Modulation of Monocytes Dampens the IL-17 + γδ T cell Response and Associated Psoriasis Pathology in Mice.

Psoriasis is a chronic inflammatory condition of the skin, autoimmune in nature, that affects millions of people worldwide. It is driven by IL-17-producing CD4 and γδ-T cells and targeted by current anti-IL-17 or anti-IL-23 monoclonal antibody therapies. These treatments are expensive, increase the risk of opportunistic infections and do not specifically target the inflammatory cascade. Other cells, including inflammatory monocytes have been shown to migrate to psoriatic plaques in both human disease and the imiquimod (IMQ)-induced mouse model and could thus constitute potential alternative therapeutic targets. In the mouse, immune modifying particles (IMP) specifically target Ly6Chi inflammatory monocytes migrating to the site of inflammation, sequestering them in the spleen. In this project, we determined whether IMP could mitigate the development of IMQ-induced psoriasis in mice. IMP treatment significantly reduced IMQ-induced psoriasis severity, decreasing dermal infiltration of Ly6Chi monocytes, as well as early stage monocyte-derived dermal macrophages. This was associated with reduced levels of hallmark cytokines IL-23 and IL-1β, as well as associated IL-17-producing γδ T cells. Our work highlights the crucial importance of inflammatory monocytes in the development of this disease, as well as a therapeutic potential for IMP in psoriasis.