Hyaluronic acid impacts the inflammatory potential and pathogenicity of autoreactive Th17 cells 3039

Abstract Description High amounts of inflammatory cytokine IL-17 expressed by autoreactive Th17 cells aid in developing and progressing autoimmune diseases. Previous studies show that Th17 cells proliferate aggressively when differentiated with IL-1?? and IL-23 or TLR2 activation and cause experimental autoimmune encephalomyelitis (EAE) in mice after adoptive transfer. Hyaluronic acid (HA) is known to accumulate in inflammatory lesions in multiple sclerosis and EAE, we aim to investigate the role of HA and its modulation in the pathogenic potential of inflammatory Th17 cells in autoimmune diseases. We demonstrate that normal Th17 cell differentiation and proliferation depend on a baseline amount of HA, and its addition increases IL-17 in Th17 cells but decreases their proliferation. Hyaluronic acid synthase overexpression in Th17 cells mimics these effects on cell phenotype and ameliorates EAE in mice following adoptive transfer. However, these effects are reversed by HA cleavage by exogenous hyaluronidase and its overexpression in Th17 cells in vitro. The adoptive transfer of hyaluronidase overexpressing Th17 cells leads to severe EAE despite a lower level of encephalitogenic cytokines. Our findings suggest that HA forms a dense glycocalyx around Th17 cells, and its modulation affects their pathogenic potential. Future research will help us understand regulation and mechanisms of Th17 pathogenicity by HA, which could potentially help to identify target molecules for treating autoimmune disorders Topic Categories Basic Autoimmunity (BA)