Unravelling the imbalanced Th17-like cell differentiation by single-cell RNA sequencing in multiple myeloma

被引:2
作者
Wan, Yike [1 ]
Jiang, Jinxing [1 ]
Chen, Mengping [1 ]
Han, Xiaofeng [1 ]
Zhong, Lu [1 ]
Xiao, Fei [1 ]
Liu, Jia [1 ]
Liu, Junling [2 ]
Li, Hua [3 ]
Huang, Honghui [1 ]
Hou, Jian [1 ]
机构
[1] Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Dept Hematol, Shanghai 200127, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China
[3] Shanghai Jiao Tong Univ, Bioid Ctr, Sch Biomed Engn, Shanghai 200240, Peoples R China
基金
中国国家自然科学基金;
关键词
Multiple myeloma; Th17-like cells; Treg cells; Imbalanced cell differentiation; Cell -cell interaction; REGULATORY T-CELLS; PLASTICITY; IMMUNITY; TARGETS;
D O I
10.1016/j.intimp.2023.110852
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Multiple myeloma (MM) is a bone marrow resident hematological malignancy. T helper (Th) cells play an essential role in maladjustment of immune function and promotion of myeloma cell proliferation and survival, which has not been fully elucidated. Here, we compared transcriptome profiles of CD4+ T cells in bone marrow samples of 3 healthy individuals and 10 MM patients before and after treatment using single-cell RNA sequencing. CD4+ T cells were divided into 7 clusters. Imbalanced Th17-like cell differentiation was indicated in MM based on bioinformation analyses, which involved IL2-STAT5 pathways and transcription factors NKFB1, RELA, STAT3, and GTF2A2. Pseudotime trajectory analysis of CD4+ T cell clusters further uncovered the enhanced transition of Th17-like to regulatory T (Treg) cells in MM, which was featured by expression changes of PLAC8, NKFB1, RELA, STAT3, and STAT1 along with the developmental path. Reduced cell-cell interaction between MM cells and CD4+ naive/recently activated naive T cells via CD74-APP might lead to imbalanced Th17-like cell differentiation. Checkpoints via TIGIT-NECTIN3 and LGALS9-CD47 in Treg and MM cells were also identified. Our study reveals imbalanced differentiation pattern of Th17-like cells and the immunosuppressive profiles in connection with MM cells, which might help to shed light on CD4+ T cell function in MM.
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页数:9
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