Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.
Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.
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DOI：
10.3390/ijms23063171
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发表时间：
2022-03-15
影响因子：
5.6
通讯作者：
Ballester S
中科院分区：
文献类型：
--
作者：
Ballester A;Guijarro A;Bravo B;Hernández J;Murillas R;Gallego MI;Ballester S
Hedgehog（Hh）通路对于胚胎发育和许多成体组织和器官的稳态维持是必需的。它还与先天性和适应性免疫系统的某些功能有关。然而，其参与免疫反应尚未得到很好的确定。在此，我们使用Ptch-1-LacZ+/−小鼠模型（以下简称为ptch+/−）研究Hh信号传导在免疫应答调节中的作用，在该模型中，Hh受体基因Patched-1的半合子失活导致Hh应答基因的组成性激活。脾和淋巴结（LN）T细胞的体外TCR刺激显示，与来自野生型（wt）同窝仔的对照细胞相比，ptch+/−细胞中Th 2细胞因子（IL-4和IL-10）水平升高，表明Hh途径激活有利于Th 2表型。此外，CD 4+细胞分泌较少的IL-17，并且在ptch+/−小鼠中Th 1表型的建立受损。一致地，在响应通过诱导实验性自身免疫性脑脊髓炎（EAE）的炎性攻击时，ptch+/−小鼠表现出比wt小鼠更温和的临床评分和更轻微的脊髓损伤。这些结果证明了Hh/ptch通路在免疫应答调节中的作用，并强调了ptch+/−小鼠模型在研究T细胞介导的疾病和寻找炎性疾病新治疗策略方面的有用性。
The Hedgehog (Hh) pathway is essential for the embryonic development and homeostatic maintenance of many adult tissues and organs. It has also been associated with some functions of the innate and adaptive immune system. However, its involvement in the immune response has not been well determined. Here we study the role of Hh signalling in the modulation of the immune response by using the Ptch-1-LacZ+/− mouse model (hereinafter referred to as ptch+/−), in which the hemizygous inactivation of Patched-1, the Hh receptor gene, causes the constitutive activation of Hh response genes. The in vitro TCR stimulation of spleen and lymph node (LN) T cells showed increased levels of Th2 cytokines (IL-4 and IL-10) in ptch+/−cells compared to control cells from wild-type (wt) littermates, suggesting that the Th2 phenotype is favoured by Hh pathway activation. In addition, CD4+ cells secreted less IL-17, and the establishment of the Th1 phenotype was impaired in ptch+/− mice. Consistently, in response to an inflammatory challenge by the induction of experimental autoimmune encephalomyelitis (EAE), ptch+/− mice showed milder clinical scores and more minor spinal cord damage than wt mice. These results demonstrate a role for the Hh/ptch pathway in immune response modulation and highlight the usefulness of the ptch+/− mouse model for the study of T-cell-mediated diseases and for the search for new therapeutic strategies in inflammatory diseases.
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影响因子：
7.5
作者：
Bravo B;Gallego MI;Flores AI;Bornstein R;Puente-Bedia A;Hernández J;de la Torre P;García-Zaragoza E;Perez-Tavarez R;Grande J;Ballester A;Ballester S
通讯作者：
Ballester S
DOI：
10.1073/pnas.1616447113
发表时间：
2016-11-22
影响因子：
11.1
作者：
Lee, John J.;Rothenberg, Michael E.;Beachy, Philip A.
通讯作者：
Beachy, Philip A.
影响因子：
--
作者：
Liu, Zhiqiang;Lai, Kun;Zhou, Xiangyu
通讯作者：
Zhou, Xiangyu
影响因子：
5.5
作者：
Caimano M;Lospinoso Severini L;Loricchio E;Infante P;Di Marcotullio L
通讯作者：
Di Marcotullio L
影响因子：
3.3
作者：
Li, Rong;Cai, Li;Hu, Xiang-yang
通讯作者：
Hu, Xiang-yang