Transcriptomic profiling of iris tissue highlights LCK signaling and T cell-mediated immunity in Behcet's uveitis

作者全名："Deng, Yang; Zhang, Yinan; Cai, Tao; Wang, Qingfeng; Zhang, Wanyun; Chen, Zhijun; Luo, Xiang; Su, Guannan; Yang, Peizeng"

作者地址："[Deng, Yang; Cai, Tao; Wang, Qingfeng; Zhang, Wanyun; Chen, Zhijun; Luo, Xiang; Su, Guannan; Yang, Peizeng] Chongqing Med Univ, Chongqing Eye Inst, Chongqing Branch Natl Clin Res Ctr Ocular Dis, Chongqing Key Lab Ophthalmol,Affiliated Hosp 1, Chongqing, Peoples R China; [Zhang, Yinan] Zhengzhou Univ, Henan Prov Eye Hosp, Dept Ophthalmol,Affiliated Hosp 1, Henan Int Joint Res Lab Ocular Immunol & Retinal I, Zhengzhou, Peoples R China; [Zhang, Yinan] Zhengzhou Univ, Acad Med Sci, Zhengzhou, Peoples R China; [Yang, Peizeng] Chongqing Med Univ, Chongqing Key Lab Ophthalmol, Affiliated Hosp 1, 1 You Yi Rd, Chongqing 400016, Peoples R China; [Yang, Peizeng] Chongqing Eye Inst, Chongqing Branch Natl Clin Res Ctr Ocular Dis, 1 You Yi Rd, Chongqing 400016, Peoples R China"

通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Ophthalmol, Affiliated Hosp 1, 1 You Yi Rd, Chongqing 400016, Peoples R China.; Yang, PZ (通讯作者)，Chongqing Eye Inst, Chongqing Branch Natl Clin Res Ctr Ocular Dis, 1 You Yi Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF AUTOIMMUNITY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000868221600002

JCR分区：Q1

影响因子：12.8

年份：2022

卷号：133

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：RNA sequencing; Behcet disease; Uveitis; T cells; LCK; Iris

摘要："Uveitis is the most common form of ocular lesions in Behcet's disease, severely affecting visual function. Mo-lecular pathological changes of ocular lesions in patients with Behcet's uveitis (BU) are largely unknown. In this study, we performed the first comprehensive transcriptomic profiling of iris specimens from BU patients and healthy donors to provide an insight into intraocular immunopathogenesis. The mRNA sequencing identified 1633 differentially expressed genes (DEGs) between the BU group and healthy controls. GO functional enrich-ment analysis on DEGs showed that T cell activation was the most significantly enriched biological process. KEGG analysis of DEGs also revealed several prominently enriched T cell-related pathways, including the T cell receptor signaling pathway, Th17 cell differentiation, and Th1 and Th2 cell differentiation. The lymphocyte -specific protein tyrosine kinase (LCK) was identified as the key hub gene in the protein interaction network of DEGs. Western blot analysis further showed increased expression of active LCK in the BU group, suggesting activation of LCK signaling. Using publicly accessible single-cell RNA-sequencing data of the healthy iris, LCK was found to be expressed in clusters of activated T cells but not in other iris cell clusters, suggesting an overt association between LCK upregulation and T cell-mediated immune dysregulation. Additionally, 16 drugs were predicted to be potential inhibitors of LCK. Overall, these findings not only highlighted the central role of T cell -mediated immunity and previously unreported LCK signaling in intraocular immunopathogenesis but also revealed the potential value of LCK as a new therapeutic target for BU patients."

基金机构："Natural Science Foundation Major International (Regional) Joint Research Project [81930023]; National Natural Science Foundation Key Program [2019]; Chongqing Outstanding Science Project [2018]; Chongqing Chief Medical Scientist Project [CSTC, 2008CA5003]; Chongqing Key Laboratory of Ophthalmology [cstc2014pt-sy10002]; Chongqing Science & Technology Platform and Base Construction Program [CSTC2021jscx-gksb-N0010]; Key Project of Chongqing Science and Technology Bureau; [81720108009]"

基金资助正文："This work was supported by the Natural Science Foundation Major International (Regional) Joint Research Project [grant numbers 81720108009] ; the National Natural Science Foundation Key Program [grant numbers 81930023] ; the Chongqing Outstanding Science Project [grant numbers 2019] ; the Chongqing Chief Medical Scientist Project [grant numbers 2018] ; the Chongqing Key Laboratory of Ophthalmology [grant numbers CSTC, 2008CA5003] ; the Chongqing Science & Technology Platform and Base Construction Program [grant numbers cstc2014pt-sy10002] ; and the Key Project of Chongqing Science and Technology Bureau [grant numbers CSTC2021jscx-gksb-N0010] . The funding organization had no role in the design or conduct of this research."