- VISTA reduces IL-9-dependent fibrosis in antibody-mediated glomerulonephritis
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Min-Gang Kim, Chae Lin Kang, Yun-Sun Lee, Su Hwan Park, Hack June Lee, Dong Ki Kim, Yon Su Kim, Dong-Sup Lee, Seung Seok Han
2020 ; 2020(1):
Glomerulonephritis | VISTA | IL-9 | Fibrosis
- 논문분류 :
- 춘계학술대회 초록집
V-domain Ig suppressor of T cell activation (VISTA), constitutively expressed in kidney-resident macrophages, participates in the repair process from ischemic renal injury. However, its role in antibody-mediated glomerulonephritis remains unresolved. C57BL/6 wild-type (WT) and Vsir (encoding VISTA)–knockout mice were treated with nephrotoxic serum to induced antibody-mediated glomerulonephritis. Cytokine and fibrosis profiles were compared between WT and Vsir–/– mice. During the glomerular injury, VISTA was primarily expressed in kidney-resident macrophages and less in kidney-infiltrating macrophages. In the early phase (i.e., day 8), Vsir–/– mice harbored higher renal T-cell infiltration and interleukin (IL)-9 levels than WT mice, and this immunological milieu in Vsir–/– mice resulted in azotemia and proteinuria. Fibrotic materials accumulated in the tubulointerstitium of Vsir–/– mice more than WT mice, and this trend remained consistent in the late phase of glomerulonephritis (i.e., day 36). VISTA in the kidney-resident macrophages reduces immunological milieu of antibody-mediated glomerulonephritis via suppression of T-cell infiltration and IL-9, which ultimately limits tubulointerstitial fibrosis.