Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis.
Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis.
复制标题
DOI：
10.1038/s41467-021-26099-w
复制
发表时间：
2021-10-12
影响因子：
16.6
通讯作者：
Sato S
中科院分区：
文献类型：
--
作者：
Kuzumi A;Yoshizaki A;Matsuda KM;Kotani H;Norimatsu Y;Fukayama M;Ebata S;Fukasawa T;Yoshizaki-Ogawa A;Asano Y;Morikawa K;Kazoe Y;Mawatari K;Kitamori T;Sato S
系统性硬化症(SSC)是一种以纤维化和自身免疫为特征的慢性多系统疾病。白介素31参与了肝纤维化和辅助性T细胞(Th)2免疫反应，这两者都是SSC的特征。IL-31在SSC发病机制中的确切作用尚不清楚。在这里，我们展示了IL-31和IL-31受体A(IL-31RA)在SSC患者的真皮成纤维细胞(DFS)中的过度表达。我们阐明了IL-31在SSC中的双重作用，其中IL-31直接促进DFS中胶原的产生，并通过增加DFS中Th2前细胞因子的表达间接增强Th2免疫应答。此外，用抗IL-31RA抗体阻断IL-31可显著改善SSC小鼠模型的纤维化和Th2极化。因此，除了将IL-31定义为SSC纤维化和Th2免疫反应的介质外，我们的研究还为在SSC的治疗中靶向IL-31/IL-31RA轴提供了理论基础。系统性硬化症(SSC)涉及多系统纤维化和自身免疫，治疗选择有限。在这里，作者证明IL-31和IL-31RA在SSC患者的皮肤成纤维细胞中过表达，并表明阻断IL-31/IL-31RA可以减少纤维化和细胞因子的释放。
Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc. Systemic sclerosis (SSc) disease involves multisystem fibrosis and autoimmunity with limited treatment options. Here the authors demonstrate that IL-31 and IL-31RA are overexpressed in dermal fibroblasts from SSc patients and show that fibrosis and cytokine release can be reduced upon blocking of IL-31/IL-31RA.
登录
查看更多内容
影响因子：
6.4
作者：
Ip, Wai K.;Wong, Chun K.;Lam, Christopher W. K.
通讯作者：
Lam, Christopher W. K.
影响因子：
3.6
作者：
Nattkemper, Leigh A.;Martinez-Escala, Maria-Estela;Yosipovitch, Gil
通讯作者：
Yosipovitch, Gil
影响因子：
27.4
作者：
FIOCCO, U;ROSADA, M;TODESCO, S
通讯作者：
TODESCO, S
DOI：
10.1084/jem.194.6.809
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Homer RJ;Zhu Z;Lanone S;Wang X;Koteliansky V;Shipley JM;Gotwals P;Noble P;Chen Q;Senior RM;Elias JA
通讯作者：
Elias JA
影响因子：
27.4
作者：
Manetti, Mirko;Ibba-Manneschi, Lidia;Cipriani, Paola
通讯作者：
Cipriani, Paola