| First Author | Kadoya H | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 19 | PubMed ID | 32870819 |
| Mgi Jnum | J:307773 | Mgi Id | MGI:6705734 |
| Doi | 10.1172/jci.insight.131252 | Citation | Kadoya H, et al. (2020) Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis. JCI Insight 5(19) |
| abstractText | Lupus nephritis (LN) is a major organ complication and cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is an unmet medical need for developing more efficient and specific, mechanism-based therapies, which depends on improved understanding of the underlying LN pathogenesis. Here we present direct visual evidence from high-power intravital imaging of the local kidney tissue microenvironment in mouse models showing that activated memory T cells originated in immune organs and the LN-specific robust accumulation of the glomerular endothelial glycocalyx played central roles in LN development. The glomerular homing of T cells was mediated via the direct binding of their CD44 to the hyaluronic acid (HA) component of the endothelial glycocalyx, and glycocalyx-degrading enzymes efficiently disrupted homing. Short-course treatment with either hyaluronidase or heparinase III provided long-term organ protection as evidenced by vastly improved albuminuria and survival rate. This glycocalyx/HA/memory T cell interaction is present in multiple SLE-affected organs and may be therapeutically targeted for SLE complications, including LN. |
