Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway

Psoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we fou...

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Main Authors: Weiwei Guo, Fengying Xu, Zhuochen Zhuang, Zhe Liu, Jiming Xie, Liping Bai
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.662362/full
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spelling doaj-3b74fca1015a45759f0661ba32da638b2021-04-26T05:29:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.662362662362Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 PathwayWeiwei Guo0Fengying Xu1Fengying Xu2Zhuochen Zhuang3Zhe Liu4Jiming Xie5Liping Bai6NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaNHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInner Mongolia Medical University, Inner Mongolia People’s Hospital, Hohhot, ChinaNHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaNHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInner Mongolia Medical University, Inner Mongolia People’s Hospital, Hohhot, ChinaNHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaPsoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we found Ebosin, a novel exopolysaccharide isolated from Streptomyces sp. 139 by our lab, not only could ameliorate inflammation in LPS-induced keratinocytes through IKK/NF-kapaB pathway, but also attenuate psoriatic skin lesions and reduce inflammatory factors expression in imiquimod (IMQ)-mediated psoriatic mice. Except for inhibiting the expression of epidermal differentiation related proteins, Ebosin significantly increased the percentage of CD4+Foxp3+CD25+ Tregs and decreased CD4+IL17A+ Th17 cells in psoriatic mice. Furthermore, we demonstrate that Ebosin significantly suppressed the IL-17 signaling pathway via A20 (encoded by tnfaip3) in vivo. As the direct binding of tnfaip3 to miR-155 has been demonstrated by luciferase reporter assay, and Ebosin has been demonstrated to inhibit miR-155 level in vitro and in vivo, our study first indicates that Ebosin reduces inflammation through the miR-155-tnfaip3-IL-17 axis and T cell differentiation in a psoriasis-like model. Thus, we conclude that Ebosin can act as a promising therapeutic candidate for the treatment of psoriasis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.662362/fullpsoriasisebosininflammationmiR-155tnfaip3
collection DOAJ
language English
format Article
sources DOAJ
author Weiwei Guo
Fengying Xu
Fengying Xu
Zhuochen Zhuang
Zhe Liu
Jiming Xie
Liping Bai
spellingShingle Weiwei Guo
Fengying Xu
Fengying Xu
Zhuochen Zhuang
Zhe Liu
Jiming Xie
Liping Bai
Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway
Frontiers in Immunology
psoriasis
ebosin
inflammation
miR-155
tnfaip3
author_facet Weiwei Guo
Fengying Xu
Fengying Xu
Zhuochen Zhuang
Zhe Liu
Jiming Xie
Liping Bai
author_sort Weiwei Guo
title Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway
title_short Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway
title_full Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway
title_fullStr Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway
title_full_unstemmed Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway
title_sort ebosin ameliorates psoriasis-like inflammation of mice via mir-155 targeting tnfaip3 on il-17 pathway
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2021-04-01
description Psoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we found Ebosin, a novel exopolysaccharide isolated from Streptomyces sp. 139 by our lab, not only could ameliorate inflammation in LPS-induced keratinocytes through IKK/NF-kapaB pathway, but also attenuate psoriatic skin lesions and reduce inflammatory factors expression in imiquimod (IMQ)-mediated psoriatic mice. Except for inhibiting the expression of epidermal differentiation related proteins, Ebosin significantly increased the percentage of CD4+Foxp3+CD25+ Tregs and decreased CD4+IL17A+ Th17 cells in psoriatic mice. Furthermore, we demonstrate that Ebosin significantly suppressed the IL-17 signaling pathway via A20 (encoded by tnfaip3) in vivo. As the direct binding of tnfaip3 to miR-155 has been demonstrated by luciferase reporter assay, and Ebosin has been demonstrated to inhibit miR-155 level in vitro and in vivo, our study first indicates that Ebosin reduces inflammation through the miR-155-tnfaip3-IL-17 axis and T cell differentiation in a psoriasis-like model. Thus, we conclude that Ebosin can act as a promising therapeutic candidate for the treatment of psoriasis.
topic psoriasis
ebosin
inflammation
miR-155
tnfaip3
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.662362/full
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