Depletion of CD8+ T Cells Exacerbates CD4+ T Cell-Induced Monocyte-to-Fibroblast Transition in Renal Fibrosis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yanjun DongJie Du

Abstract

Bone marrow-derived monocyte-to-fibroblast transition is a key step in renal fibrosis pathogenesis, which is regulated by the inflammatory microenvironment. However, the mechanism by which the inflammatory microenvironment regulates this transition is not fully understood. In this study, we examined how the CD8(+) T cell/IFN-γ microenvironment regulates the monocyte-to-fibroblast transition in renal fibrosis. Genetic ablation of CD8 promoted a monocyte-to-fibroblast transition and increased renal interstitial fibrosis, whereas reconstitution of CD8 knockout (KO) mice with CD8(+) T cells decreased fibrosis. However, depletion of CD4(+) T cells in CD8 KO mice also reduced fibrosis. To elucidate the role of CD4(+) T cells in mediating CD8-regulated monocyte-to-fibroblast transition, CD4(+) T cells were isolated from obstructed kidneys of CD8 KO or wild-type mice. CD4(+) T cells isolated from CD8 KO obstructed kidney expressed more IL-4 and GATA3 and less IFN-γ and T-bet and showed increased monocyte-to-fibroblast transition in vitro compared with those isolated from wild-type obstructed kidney. To examine the role of IFN-γ-expressing CD8(+) T cells, we reconstituted CD8 KO mice with CD8(+) T cells isolated from IFN-γ KO mice. The ...Continue Reading

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Dec 28, 2016·International Journal of Molecular Sciences·Haidong WangYanjun Dong
Jan 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yan LiJinghong Zhao
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May 30, 2021·Journal of the American Society of Nephrology : JASN·Sophia Sears, Leah Siskind

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