Cutting edge: c-Kit signaling differentially regulates type 2 innate lymphoid cell accumulation and susceptibility to central nervous system demyelination in male and female SJL mice.
Cutting edge: c-Kit signaling differentially regulates type 2 innate lymphoid cell accumulation and susceptibility to central nervous system demyelination in male and female SJL mice.
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DOI：
10.4049/jimmunol.1500068
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发表时间：
2015-06-15
期刊：
影响因子：
--
通讯作者：
Brown MA
中科院分区：
文献类型：
--
作者：
Russi AE;Walker-Caulfield ME;Ebel ME;Brown MA
多发性硬化症（MS）优先影响女性，这种性别二态性在SJL小鼠MS模型（实验性自身免疫性脑脊髓炎（EAE））中重现。在这里，我们证明了通过c-kit信号传导对雄性和雌性SJL小鼠的EAE易感性产生不同的影响。先前在雌性中的研究表明，Kit突变型（W/Wv）小鼠比野生型小鼠对EAE的易感性更低。然而，雄性W/Wv小鼠表现出加重的疾病，这是一种不依赖于肥大细胞的表型，对应于从Th 2为主的T细胞应答向Th 17为主的T细胞应答转变。我们证明了以前未描述的赤字c-kit+2型先天淋巴细胞（ILC 2）在W/Wv小鼠。ILC 2在EAE易感的WT雌性中也显著减少，表明ILC 2功能需要c-kit信号和未定义的雄性特异性因子。我们认为，Th 2促进ILC 2的缺陷消除了致脑炎性T细胞反应的衰减影响，因此增加了疾病的易感性。
Multiple sclerosis (MS) preferentially affects women and this sex dimorphism is recapitulated in the SJL mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that signaling through c-kit exerts distinct effects on EAE susceptibility in male and female SJL mice. Previous studies in females show that Kit mutant (W/Wv) mice are less susceptible to EAE than wildtype mice. However, male W/Wv mice exhibit exacerbated disease, a phenotype independent of mast cells and corresponding to a shift from a Th2 to a Th17 dominated T cell response. We demonstrate a previously undescribed deficit in c-kit+ type 2 innate lymphoid cells (ILC2s) in W/Wv mice. ILC2s are also significantly reduced in EAE-susceptible WT females indicating that both c-kit signals and undefined male-specific factors are required for ILC2 function. We propose that deficiencies in Th2-promoting ILC2s removes an attenuating influence on the encephalitogenic T cell response and therefore increases disease susceptibility.
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影响因子：
4.4
作者：
Sayed, Blayne A.;Christy, Alison L.;Brown, Melissa A.
通讯作者：
Brown, Melissa A.
影响因子：
9.6
作者：
Halim, Timotheus Y. F.;McKenzie, Andrew N. J.
通讯作者：
McKenzie, Andrew N. J.
影响因子：
4.4
作者：
Milovanovic, Marija;Volarevic, Vladislav;Lukic, Miodrag L.
通讯作者：
Lukic, Miodrag L.
影响因子：
4.4
作者：
Rostami, Abdolmohamad;Ciric, Bogoljub
通讯作者：
Ciric, Bogoljub
在多发性硬化症的鼠模型中，肥大细胞对于早期发作和严重疾病至关重要。
影响因子：
15.3
作者：
Secor, V H;Secor, W E;Gutekunst, C A;Brown, M A
通讯作者：
Brown, M A