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DOI	10.1073/pnas.2023230118
	ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1
	Umeda M.; Yoshida N.; Hisada R.; Burbano C.; Orite S.Y.K.; Kono M.; Kyttaris V.C.; Krishfield S.; Owen C.A.; Tsokos G.C.
发表日期	2021
ISSN	00278424
卷号	118 期号:18
英文摘要	The a disintegrin and metalloproteinase (ADAM) family of proteinases alter the extracellular environment and are involved in the development of T cells and autoimmunity. The role of ADAM family members in Th17 cell differentiation is unknown. We identified ADAM9 to be specifically expressed and to promote Th17 differentiation. Mechanistically, we found that ADAM9 cleaved the latency-associated peptide to produce bioactive transforming growth factor β1, which promoted SMAD2/3 phosphorylation and activation. A transcription factor inducible cAMP early repressor was found to bind directly to the ADAM9 promoter and to promote its transcription. Adam9-deficient mice displayed mitigated experimental autoimmune encephalomyelitis, and transfer of Adam9-deficient myelin oligodendrocyte globulin-specific T cells into Rag1−/− mice failed to induce disease. At the translational level, an increased abundance of ADAM9 levels was observed in CD4+ T cells from patients with systemic lupus erythematosus, and ADAM9 gene deletion in lupus primary CD4+ T cells clearly attenuated their ability to differentiate into Th17 cells. These findings revealed that ADAM9 as a proteinase provides Th17 cells with an ability to activate transforming growth factor β1 and accelerates its differentiation, resulting in aberrant autoimmunity. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	A disintegrin and metalloproteinase; Systemic lupus erythematosus; Th17 cell
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179694
作者单位	Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Umeda M.,Yoshida N.,Hisada R.,et al. ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1[J],2021,118(18).
APA	Umeda M..,Yoshida N..,Hisada R..,Burbano C..,Orite S.Y.K..,...&Tsokos G.C..(2021).ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1.Proceedings of the National Academy of Sciences of the United States of America,118(18).
MLA	Umeda M.,et al."ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021).