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...

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Autores principales:	Chen-Hsueh Pai, Shu-Rung Lin, Chia-Hao Liu, Szu-Yu Pan, Hao Hsu, Yi-Ting Chen, Ching-Tzu Yen, I-Shing Yu, Hua-Lin Wu, Shuei-Liong Lin, Shu-Wha Lin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/965920586e02498b8ac147fc3cb3b83b
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spelling	oai:doaj.org-article:965920586e02498b8ac147fc3cb3b83b2021-12-02T18:37:06ZTargeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis10.1038/s41598-020-73194-x2045-2322https://doaj.org/article/965920586e02498b8ac147fc3cb3b83b2020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-73194-xhttps://doaj.org/toc/2045-2322Abstract 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.Chen-Hsueh PaiShu-Rung LinChia-Hao LiuSzu-Yu PanHao HsuYi-Ting ChenChing-Tzu YenI-Shing YuHua-Lin WuShuei-Liong LinShu-Wha LinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen-Hsueh Pai Shu-Rung Lin Chia-Hao Liu Szu-Yu Pan Hao Hsu Yi-Ting Chen Ching-Tzu Yen I-Shing Yu Hua-Lin Wu Shuei-Liong Lin Shu-Wha Lin Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
description	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.
format	article
author	Chen-Hsueh Pai Shu-Rung Lin Chia-Hao Liu Szu-Yu Pan Hao Hsu Yi-Ting Chen Ching-Tzu Yen I-Shing Yu Hua-Lin Wu Shuei-Liong Lin Shu-Wha Lin
author_facet	Chen-Hsueh Pai Shu-Rung Lin Chia-Hao Liu Szu-Yu Pan Hao Hsu Yi-Ting Chen Ching-Tzu Yen I-Shing Yu Hua-Lin Wu Shuei-Liong Lin Shu-Wha Lin
author_sort	Chen-Hsueh Pai
title	Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
title_short	Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
title_full	Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
title_fullStr	Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
title_full_unstemmed	Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis
title_sort	targeting fibroblast cd248 attenuates ccl17-expressing macrophages and tissue fibrosis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/965920586e02498b8ac147fc3cb3b83b
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Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis

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