ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO917

Lymphangiogenesis Within Kidney and Its Draining Lymph Nodes Mediates Renal Inflammation and Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Guangchang, Pei, Tongji Hospital, Tongji Medical College, Huazhong 9 University of Science and Technology, Wuhan, China
  • Zeng, Rui, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HuBei , China
  • Xu, Gang, Tongji Hospital, Tongji Medical College, Huazhong 9 University of Science and Technology, Wuhan, China
Background

Lymphangiogenesis has been reported in kidney transplant and chronic kidney diseases (CKD). Here, we demonstrate a crucial role for the newborn lymphatic vessels (LVs) within kidney and its draining lymph nodes (RDLNs) in driving intrarenal inflammation and fibrosis.

Methods

In the present study, we examined the lymphangiogenesis within kidney and RDLNs in different renal interstitial fibrosis models. Conditional knockdown of LVs in LYVE-1-Cre/iDTR mice and knockdown of lymphangiogenesis by sVEGFR3-FC or sLYVE-1-FC were adopted to observe the relationship between LVs with renal inflammation and fibrosis. CCR7 neutralizing antibody were used to blocking CCR7/CCL21, to further explore the role of CCR7/CCL21 in immunocytes recruitment.

Results

Lymphangiogenesis occurs in kidney and its DLNs after renal injury, which mainly results from the local proliferation of pre-existing lymphatic endothelium. The newborn LVs like the inherent LVs essentially express C-C chemokine ligand 21 (CCL21).The expansive LVs system play an important role in the recruitment of more CCR7+ dendritic cells(DCs) and lymphocytes into RDLNs and spleen, and finally inducing systemic lymphocyte expansion. Blocking CCR7+ cell recruitment into RDLNs and spleen by genetically or biologically knockdown of LVs, or inhibiting CCR7+ cell expansion using CCR7 neutralizing antibody, attenuated intrarenal inflammation and fibrosis.

Conclusion

We show a previously unidentified role for lymphangiogenesis in regulating intrarenal inflammation and fibrosis, which uncovered novel strategies for preventing CKD progression.

Funding

  • Government Support - Non-U.S.