@article{cf3b7f7b36344701ba55eb4cbc2e8f71,
title = "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.",
author = "Pai, {Chen Hsueh} and Lin, {Shu Rung} and Liu, {Chia Hao} and Pan, {Szu Yu} and Hao Hsu and Chen, {Yi Ting} and Yen, {Ching Tzu} and Yu, {I. Shing} and Wu, {Hua Lin} and Lin, {Shuei Liong} and Lin, {Shu Wha}",
note = "Funding Information: Dr. David Brenner (Univ. California, San Diego, CA) for Col1a1-GFPTg mice, Dr. Masaru Okabe and Dr. Masa-hito Ikawa (Osaka Univ., Osaka, Japan) for GFPTg mice, Dr. Fu-Tong Liu (Academia Sinica, Taipei, Taiwan) for Lgals3-/- mice, Dr. Gordan Dougan (Imperial College of Science, Technology and Medicine, UK) for plasmid DNA expressing C fragment of tetanus toxoid, the Department of Medical Research of National Taiwan University Hospital (NTUH) for equipment support, the Cell Sorting Core Facility of the First Core Laboratory, the Transgenic Mouse Model Core Facility of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology (MOST), Taiwan and the Gene Knockout Mouse Core Laboratory of National Taiwan University (NTU) Center of Genomic and Precision Medicine. S.R.L. is supported by Ministry of Science and Technology, Taiwan (MOST, 102-2320-B-033-003, 102-2632-M-033-001-MY3, 105-2320-B-033-003). S.Y.P. is supported by MOST (106-2314-B-418-006, 107-2314-B-418-001, 108-2314-B-418-004) and Far-Eastern Memorial Hospital (2017-C-037, 2020-C-037). Y.T.C. is supported by MOST (107-2314-B-002-019, 108-2314-B-002-071-MY2). S.L.L. is supported by MOST (105-2314-B-002-096-MY3, 107-2314-B-002-078-, 108-2314-B-002-012, 108-2314-B-002-078-MY3, 109-2314-B-002-260-), National Health Research Institutes (EX106-10633SI, EX107-10633SI, EX108-10633SI), NTUH (107-T02, 108-T16, 109-T16), NTUH and NTU College of Medicine (NSCCMOH-131-43), Taiwan Health Foundation and Mrs. Hsiu-Chin Lee Kidney Research Foundation. S.W.L. is supported by MOST (105-2319-B-002-001, 105-2320-B-002-052-MY3, 105-2320-B-002-053-MY3, 106-2319-B-002-001, 107-2319-B-002-001). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-73194-x",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}