| Autor: |
Millrine, David, Haruhiko Miyata, Mami Tei, Dubey, Praveen, Nyati, Kishan, Taisuke Nakahama, Yohannes Gemechu, Ripley, Barry, Tadamitsu Kishimoto |
| Předmět: |
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| Zdroj: |
International Immunology; Jun2016, Vol. 28 Issue 6, p307-315, 9p |
| Abstrakt: |
Thalidomide and its derivatives, collectively referred to as immunomodulatory drugs (IMiDs), are effective inhibitors of inflammation and are known to inhibit TLR-induced TNFα production. The identification of Cereblon as the receptor for these compounds has led to a rapid advancement in our understanding of IMiD properties; however, there remain no studies addressing the role of Cereblon in mediating the suppressive effect of IMiDs on TLR responses. Here, we developed Cereblon-deficient mice using the CRISPR-Cas9 system. TLR-induced cytokine responses were unaffected by Cereblon deficiency in vivo. Moreover, IMiD treatment inhibited cytokine production even in the absence of Cereblon. The IMiD-induced suppression of cytokine production therefore occurs independently of Cereblon in mice. Further investigation revealed that IMiDs are potent inhibitors of TLR-induced type-1 interferon production via suppression of the TRIF/IRF3 pathway. These data suggest that IMiDs may prove effective in the treatment of disorders characterized by the ectopic production of type-1 interferon. Significantly, these properties are mediated separately from thalidomide's teratogenic receptor, Cereblon. Thus, certain therapeutic properties of Thalidomide can be separated from its harmful side effects. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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