PIM kinases regulate early human Th17 cell differentiation

Tanja Buchacher; Ankitha Shetty; Saara A. Koskela; Johannes Smolander; Riina Kaukonen; António G.G. Sousa; Sini Junttila; Asta Laiho; Olof Rundquist; Tapio Lönnberg; Alexander Marson; Omid Rasool; Laura L. Elo; Riitta Lahesmaa

Cell Reports (Dec 2023)

PIM kinases regulate early human Th17 cell differentiation

Tanja Buchacher,
Ankitha Shetty,
Saara A. Koskela,
Johannes Smolander,
Riina Kaukonen,
António G.G. Sousa,
Sini Junttila,
Asta Laiho,
Olof Rundquist,
Tapio Lönnberg,
Alexander Marson,
Omid Rasool,
Laura L. Elo,
Riitta Lahesmaa

Affiliations

Tanja Buchacher: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Corresponding author
Ankitha Shetty: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
Saara A. Koskela: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland
Johannes Smolander: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Riina Kaukonen: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
António G.G. Sousa: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Sini Junttila: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Asta Laiho: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Olof Rundquist: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Tapio Lönnberg: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Alexander Marson: Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Omid Rasool: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Laura L. Elo: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland
Riitta Lahesmaa: Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland; Corresponding author

Journal volume & issue: Vol. 42, no. 12
p. 113469

Abstract

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Summary: 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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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