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Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis.


ABSTRACT: The role of fibroblasts in tissue fibrosis has been extensively studied. Activated fibroblasts, namely myofibroblasts, produce pathological extracellular matrix. CD248, a type I transmembrane glycoprotein, is expressed in fibroblasts after birth. In human chronic kidney disease, upregulated CD248 in myofibroblasts is linked to poor renal survival. In this study, we demonstrated a novel interaction between CD248 and macrophages to be a key step in mediating tissue fibrosis. CD248 was upregulated in myofibroblasts in murine models of renal and peritoneal fibrosis. Cd248 knockout (Cd248-/-) could attenuate both renal and peritoneal fibrosis. By parabiosis of GFP reporter mice and Cd248-/- mice, we showed that attenuation of renal fibrosis was associated with a decrease of macrophage infiltration in Cd248-/- mice. Moreover, decrease of chemokine (C-C motif) ligand 17 and Ccl22 was found in macrophages isolated from the fibrotic kidneys of Cd248-/- mice. Because galectin-3-deficient macrophages showed decreased Ccl17 and Ccl22 in fibrotic kidneys, we further demonstrated that CD248 interacted specifically with galectin-3 of macrophages who then expressed CCL17 to activate collagen production in myofibroblasts. Mice with DNA vaccination targeting CD248 showed decreased fibrosis. We thus propose that CD248 targeting should be studied in the clinical tissue fibrosis setting.

SUBMITTER: Pai CH 

PROVIDER: S-EPMC7544830 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis.

Pai Chen-Hsueh CH   Lin Shu-Rung SR   Liu Chia-Hao CH   Pan Szu-Yu SY   Hsu Hao H   Chen Yi-Ting YT   Yen Ching-Tzu CT   Yu I-Shing IS   Wu Hua-Lin HL   Lin Shuei-Liong SL   Lin Shu-Wha SW  

Scientific reports 20201008 1


The role of fibroblasts in tissue fibrosis has been extensively studied. Activated fibroblasts, namely myofibroblasts, produce pathological extracellular matrix. CD248, a type I transmembrane glycoprotein, is expressed in fibroblasts after birth. In human chronic kidney disease, upregulated CD248 in myofibroblasts is linked to poor renal survival. In this study, we demonstrated a novel interaction between CD248 and macrophages to be a key step in mediating tissue fibrosis. CD248 was upregulated  ...[more]

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