The Protective Effects of IL-31RA Deficiency During Bleomycin-Induced Pulmonary Fibrosis.
The Protective Effects of IL-31RA Deficiency During Bleomycin-Induced Pulmonary Fibrosis.
复制标题
IL-31RA缺乏对博莱霉素性肺纤维化的保护作用
DOI：
10.3389/fimmu.2021.645717
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Madala SK
中科院分区：
文献类型：
--
作者：
Yombo DJK;Odayar V;Gupta N;Jegga AG;Madala SK
Idiopathic Pulmonary Fibrosis (IPF) is a severe fibrotic lung disease characterized by excessive collagen deposition and progressive decline in lung function. Th2 T cell-derived cytokines including IL-4 and IL-13 have been shown to contribute to inflammation and fibrotic remodeling in multiple tissues. Interleukin-31 (IL-31) is a newly identified cytokine that is predominantly produced by CD4 Th2 T cells, but its signaling receptor IL-31RA is primarily expressed by non-hematopoietic cells. However, the potential role of the IL-31-IL31RA axis in pulmonary inflammation and fibrosis has remained largely unknown. To determine the role of IL-31RA deficiency in pulmonary fibrosis, wildtype, and IL-31RA knockout mice were treated with bleomycin and measured changes in collagen deposition and lung function. Notably, the loss of IL-31 signaling attenuated collagen deposition and lung function decline during bleomycin-induced pulmonary fibrosis. The total lung transcriptome analysis showed a significant reduction in fibrosis-associated gene transcripts including extracellular matrix and epithelial cell-associated gene networks. Furthermore, the lungs of human IPF showed an elevated expression of IL-31 when compared to healthy subjects. In support, the percentage of IL-31 producing CD4+ T cells was greater in the lungs and PBMCs from IPF patients compared to healthy controls. Our findings suggest a pathogenic role for IL-31/IL-31RA signaling during bleomycin-induced pulmonary fibrosis. Thus, therapeutic targeting the IL-31-IL-31RA axis may prevent collagen deposition, improve lung function, and have therapeutic potential in pulmonary fibrosis.
登录
查看更多内容
DOI：
10.1152/ajplung.00144.2019
发表时间：
2020-07-01
影响因子：
4.9
作者：
Hudock, Kristin M.;Collins, Margaret S.;Clancy, John Paul
通讯作者：
Clancy, John Paul
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：
4.4
作者：
Bilsborough, Janine;Mudri, Sherri;Dillon, Stacey R.
通讯作者：
Dillon, Stacey R.
影响因子：
5.2
作者：
Kasam, Rajesh K.;Gajjala, Prathibha R.;Madala, Satish K.
通讯作者：
Madala, Satish K.
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG