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Roles of Ubiquitin Sensor ABIN-1 In ...
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Callahan, Joseph Aaron.
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Roles of Ubiquitin Sensor ABIN-1 In The Immune System.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
Roles of Ubiquitin Sensor ABIN-1 In The Immune System./
Author:
Callahan, Joseph Aaron.
Description:
130 p.
Notes:
Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
Contained By:
Dissertation Abstracts International75-02B(E).
Subject:
Biology, Cell. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3599369
ISBN:
9781303486067
Roles of Ubiquitin Sensor ABIN-1 In The Immune System.
Callahan, Joseph Aaron.
Roles of Ubiquitin Sensor ABIN-1 In The Immune System.
- 130 p.
Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
Thesis (Ph.D.)--University of California, San Francisco, 2013.
Heterologous expression of ABIN-1 (A20 Binding and Inhibitor of NF-kappaB-1, gene name Tnip1), like A20, was suggested to restrict TNF-induced inflammation and cell death. ABIN-1's physiological function was unknown. To interrogate ABIN-1's roles in vivo, we generated ABIN-1-deficient mice. ABIN-1 was required for successful embryonic development. TNF-deficiency rescued this lethality, demonstrating that ABIN-1 restricts potentially lethal TNF-induced signals. ABIN-1-/- TNF-/- mice develop a striking immune phenotype, suggesting that ABIN-1 restricts TNF-independent signals. ABIN-1-/- TNF-/- RAG-1-/- mice have splenomegaly, which supports that ABIN-1 expression in innate cells preserves immune quiescence. ABIN-1-/- fetal liver chimera develop partially cell-intrinsic widespread immune activation, suggesting that ABIN-1-/- hematopoietic cells are sufficient for exaggerated immune activation.
ISBN: 9781303486067Subjects--Topical Terms:
1017686
Biology, Cell.
Roles of Ubiquitin Sensor ABIN-1 In The Immune System.
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130 p.
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Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
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Adviser: Averil Ma.
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Thesis (Ph.D.)--University of California, San Francisco, 2013.
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Heterologous expression of ABIN-1 (A20 Binding and Inhibitor of NF-kappaB-1, gene name Tnip1), like A20, was suggested to restrict TNF-induced inflammation and cell death. ABIN-1's physiological function was unknown. To interrogate ABIN-1's roles in vivo, we generated ABIN-1-deficient mice. ABIN-1 was required for successful embryonic development. TNF-deficiency rescued this lethality, demonstrating that ABIN-1 restricts potentially lethal TNF-induced signals. ABIN-1-/- TNF-/- mice develop a striking immune phenotype, suggesting that ABIN-1 restricts TNF-independent signals. ABIN-1-/- TNF-/- RAG-1-/- mice have splenomegaly, which supports that ABIN-1 expression in innate cells preserves immune quiescence. ABIN-1-/- fetal liver chimera develop partially cell-intrinsic widespread immune activation, suggesting that ABIN-1-/- hematopoietic cells are sufficient for exaggerated immune activation.
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Aberrant immune activation contributes to the pathogenesis of multiple autoimmune and inflammation-exacerbated diseases. The Tnip1 gene is strongly associated with susceptibility to psoriasis in humans. Psoriasis is a chronic, inflammatory skin disease caused by a combination of environmental and genetic factors. We demonstrated that mice lacking ABIN-1 specifically in dendritic cells (DCs), ABIN-1Flox CD11c-Cre mice, exhibited perturbed immune homeostasis. ABIN-1 deficient DCs displayed exaggerated NF-kappaB-1 and MAP kinase signaling and produced more IL-23 than normal cells in response to TLR ligands. Challenge of ABIN-1Flox CD11c-Cre mice with topical TLR7 ligand lead to greater numbers of TH17 and TCRgamma/delta+ T cells and exacerbated development of psoriaform lesions. These phenotypes were reversed by DC-specific deletion of the TLR adaptor MyD88. These studies link ABIN-1 with IL-23 and IL-17, and provide cellular and molecular mechanisms by which ABIN-1 regulates susceptibility to psoriasis. They support that ubiquitin sensor ABIN-1 regulates cell survival and restricts proinflammatory signals in DC to protect against psoriasis.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3599369
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