PIM kinases regulate early human Th17 cell differentiation

被引：5
作者：
Buchacher, Tanja [1 ,2 ]
Shetty, Ankitha [1 ,2 ,3 ]
Koskela, Saara A. [1 ,2 ,4 ]
Smolander, Johannes [1 ,2 ]
Kaukonen, Riina [1 ,2 ]
Sousa, Antonio G. G. [1 ,2 ]
Junttila, Sini [1 ,2 ]
Laiho, Asta [1 ,2 ]
Rundquist, Olof [1 ,2 ]
Lonnberg, Tapio [1 ,2 ]
Marson, Alexander [5 ,6 ]
Rasool, Omid [1 ,2 ]
L., Laura [1 ,2 ,4 ]
Lahesmaa, Riitta [1 ,2 ,4 ]
机构：
[1] Univ Turku, Abo Akad Univ, Turku Biosci Ctr, Turku 20520, Finland
[2] Univ Turku, InFLAMES Res Flagship Ctr, Turku 20520, Finland
[3] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[4] Univ Turku, Inst Biomed, Turku 20520, Finland
[5] Gladstone UCSF Inst Genom Immunol, San Francisco, CA 94158 USA
[6] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
来源：
CELL REPORTS | 2023年 / 42卷 / 12期
基金：
芬兰科学院; 欧盟地平线“2020”;
关键词：
PROPROTEIN CONVERTASE FURIN; EXPRESSION ANALYSIS; T-CELLS; C-MYC; TRANSCRIPTION; MUTATIONS; FAMILY; STAT3; ACTIVATION; T-HELPER-1;
D O I：
10.1016/j.celrep.2023.113469
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The serine/threonine-specific Moloney murine leukemia virus (PIM) kinase family (i.e., PIM1, PIM2, and PIM3) has been extensively studied in tumorigenesis. PIM kinases are downstream of several cytokine signaling pathways that drive immune-mediated diseases. Uncontrolled T helper 17 (Th17) cell activation has been associated with the pathogenesis of autoimmunity. However, the detailed molecular function of PIMs in human Th17 cell regulation has yet to be studied. In the present study, we comprehensively investigated how the three PIMs simultaneously alter transcriptional gene regulation during early human Th17 cell differentiation. By combining PIM triple knockdown with bulk and scRNA-seq approaches, we found that PIM deficiency promotes the early expression of key Th17-related genes while suppressing Th1-lineage genes. Further, PIMs modulate Th cell signaling, potentially via STAT1 and STAT3. Overall, our study highlights the inhibitory role of PIMs in human Th17 cell differentiation, thereby suggesting their association with autoimmune phenotypes.
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页数：20
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