Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis
In: JCI Insight, Jg. 5 (2020-10-02), Heft 19
Online
unknown
Zugriff:
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.
A combined immunology and renal pathophysiology study of the local kidney tissue microenvironment in lupus identifies a key role of glomerular endothelial glycocalyx in disease development.
Titel: |
Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis
|
---|---|
Autor/in / Beteiligte Person: | Yu, Ning ; Kidokoro, Kengo ; Peti-Peterdi, János ; Gyarmati, Georgina ; Kadoya, Hiroyuki ; Jacob, Chaim O. ; Riquier-Brison, Anne ; Ina Maria Schiessl ; Butler, Matthew J. ; Desposito, Dorinne |
Link: | |
Zeitschrift: | JCI Insight, Jg. 5 (2020-10-02), Heft 19 |
Veröffentlichung: | American Society for Clinical Investigation, 2020 |
Medientyp: | unknown |
ISSN: | 2379-3708 (print) |
DOI: | 10.1172/jci.insight.131252 |
Schlagwort: |
|
Sonstiges: |
|