2011 Fiscal Year Final Research Report
Elucidation of the regulatory mechanisms for balancing TLR7 and TLR9 responses by UNC93b1
| Project/Area Number |
21590528
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | Toll-like receptor / 核酸認識 / ノックインマウス / LC-Ms/Ms解析 |
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| Research Abstract |
We revealed that we have a mechanism for balancing TLR9 response as a DNA sensor and TLR7 response as a RNA sensor. We identified the PDZ binding domain in N terminal region of UNC93b1 regulating the balance. We established knock-in mice for disrupting the PDZ binding domain by single amino-acid substitution. TLR7 response significantly increases and TLR9 response decreases in the Knock-in mice. Around 75% of the Knock-in mice died within a year. The mice have systemic inflammation with splenomegaly. TLR7 knockout and UNC93b1 knock-in mice are no phenotype. This result indicates that TLR7 plays an important role for the systemic inflammation. We revealed the importance of negative regulatory mechanism via PDZ binding domain in UNC93b1 in vivo. We also identified a functional UNC93b1 binding protein to regulate TLR7 and TLR9 responses.
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[Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating TLR7-and TLR9-trafficking2011
Author(s)
Fukui R, Saitoh S, Kanno A, Onji M, Shibata T, Ito A, Onji M, Matsumoto M, Akira S, YoshidaN, & Miyake K
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Journal Title
Immunity
Volume: 35
Pages: 69-81
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