Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.
Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.
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DOI：
10.4049/jimmunol.1103760
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发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Tenner AJ
中科院分区：
文献类型：
--
作者：
Benoit ME;Clarke EV;Morgado P;Fraser DA;Tenner AJ
Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like auto-immune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. Here, we developed an autologous system using primary human lymphocytes and monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I interferons (IFNs), IL-27 and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with AL conditioned media. Co-incubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose dependent manner and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1 dependent cleavage of IL-1β suggesting potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation providing potential therapeutic targets to control macrophage polarization, and thus inflammation and autoimmunity.
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影响因子：
2.9
作者：
Khoury MK;Parker I;Aswad DW
通讯作者：
Aswad DW
影响因子：
4.4
作者：
DIETZSCHOLD, B;SCHWAEBLE, W;WEIHE, E
通讯作者：
WEIHE, E
影响因子：
5.5
作者：
Fraser, Deborah A.;Bohlson, Suzanne S.;Tenner, Andrea J.
通讯作者：
Tenner, Andrea J.
影响因子：
4.6
作者：
Gullstrand, B.;Martensson, U.;Truedsson, L.
通讯作者：
Truedsson, L.
DOI：
10.1523/jneurosci.3932-10.2011
发表时间：
2011-03-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Benoit ME;Tenner AJ
通讯作者：
Tenner AJ