Distinct roles of adenylyl cyclase VII in regulating the immune responses in mice.
Distinct roles of adenylyl cyclase VII in regulating the immune responses in mice.
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DOI：
10.4049/jimmunol.0903474
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Jiang LI
中科院分区：
文献类型：
--
作者：
Duan B;Davis R;Sadat EL;Collins J;Sternweis PC;Yuan D;Jiang LI
第二信使cAMP在调节免疫应答中起关键作用。虽然众所周知其免疫抑制作用，cAMP也是最佳免疫反应的发展所必需的。因此，这第二信使的调节需要以依赖于上下文的方式进行微调和良好平衡。为了进一步了解cAMP合成在免疫系统功能中的作用，我们专注于一种特异性腺苷酸环化酶（AC）亚型，AC VII（AC 7），它在免疫系统中高度表达。我们发现，AC 7缺乏的小鼠对LPS诱导的内毒素休克过敏。AC 7缺陷小鼠的巨噬细胞对LPS产生更多的促炎细胞因子TNF-α。不能产生细胞内cAMP响应血清因子，如溶血磷脂酸，是这种表型的一个潜在原因。因此，AC 7的功能是控制针对细菌感染的免疫应答的程度。然而，它也是适应性免疫应答期间B和T细胞的最佳功能所必需的。AC 7是调节B和T细胞中cAMP合成的主要同种型。AC 7缺陷型小鼠显示出对T细胞非依赖性和T细胞依赖性Ag的受损Ab应答。记忆T细胞的产生也减少了。这些结果是第一个归因于特定功能的AC亚型在免疫系统中，并强调cAMP合成的重要性，通过这种亚型在塑造免疫反应。
The second messenger cAMP plays a critical role in regulating immune responses. Although well known for its immunosuppressive effect, cAMP is also required for the development of optimal immune responses. Thus, the regulation of this second messenger needs to be finely tuned and well balanced in a context dependent manner. To further understand the role of cAMP synthesis in the functions of the immune system, we focus on a specific adenylyl cyclase (AC) isoform, AC VII (AC7), which is highly expressed in the immune system. We show that mice deficient of AC7 are hypersensitive to LPS-induced endotoxic shock. Macrophages from AC7-deficient mice produce more of the proinflammatory cytokine, TNF-α, in response to LPS. The inability to generate intracellular cAMP response to serum factors, such as lysophosphatidic acid, is a potential cause for this phenotype. Thus, AC7 functions to control the extent of immune responses toward bacterial infection. However, it is also required for the optimal functions of B and T cells during adaptive immune responses. AC7 is the major isoform that regulates cAMP synthesis in both B and T cells. AC7-deficient mice display compromised Ab responses toward both T cell-independent and T cell-dependent Ags. The generation of memory T cells is also reduced. These results are the first to ascribe specific functions to an AC isoform in the immune system and emphasize the importance of cAMP synthesis by this isoform in shaping the immune responses.
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影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
56.9
作者：
Li, LS;Yee, C;Beavo, JA
通讯作者：
Beavo, JA
DOI：
10.1073/pnas.122041599
发表时间：
2002-05-28
影响因子：
11.1
作者：
Jin, SLC;Conti, M
通讯作者：
Conti, M
影响因子：
4.4
作者：
Kasprowicz, DJ;Kohm, AP;Sanders, VM
通讯作者：
Sanders, VM
影响因子：
21.3
作者：
Natarajan, Madhusudan;Lin, Keng-Mean;Ranganathan, Rama
通讯作者：
Ranganathan, Rama