Abstract: TH-PO917
Lymphangiogenesis Within Kidney and Its Draining Lymph Nodes Mediates Renal Inflammation and Fibrosis
Session Information
- Molecular Mechanisms of CKD - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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.