Year: 2025
Type: article
Abstract: Description Intracellular signaling factors are important targets for immunosuppressive drugs. We report a selective induction of the serine/threonine kinase Provirus Integration site for Moloney murine leukemia virus 3 (PIM3), but not its homologs PIM1 and PIM2, in activated human T cells. Specific pharmacological inhibition and CRISPR/Cas9-mediated knockout of PIM3 in primary human T cells within 2D and 3D cell culture models uncovered essential roles of this kinase in regulating T cell proliferation, viability, migration, metabolic activity, and cytotoxicity. Furthermore, PIM3 inhibition resulted in immunosuppressive effects in human immune organoids. Mass spectrometry-based target protein identification coupled with genome engineering revealed that PIM3 targets the Nucleolar protein Interacting with the FHA domain of MKI67 (NIFK) to control T cell proliferation, establishing a novel regulatory circuit that could be targeted therapeutically in conditions involving T cell hyperproliferation. Elevated PIM3 expression was detected in pathologic T cell infiltrates in human patients and pre-clinical models. Together, these findings identify PIM3 as a promising new target for immunosuppressive therapies. Funding Sources Supported by the Austrian Science Funds (FWF) project P34728-B Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
Source: The Journal of Immunology
Authors: Tobias Frey, Kristin Schaffer, Marlene Gerner, Simone Allram, Viola Baur, Alexandra Tsal-Tsalko, Anja Wagner, Johanna M. Strobl, Marlene Hollenstein, Doris Trapin, Tarik Shoumariyeh, Johannes Kovarik, Bernhard Jank, Nicholes Campion, Julia Eckl-Dorna, Gottfried Fischer, Ci Zhu, Lukas W Unger, Winfried F. Pickl, Hannes Kühtreiber, Kamil Mieczkowski, Michael Mildner, Franziska Dengler, Wilfried Ellmeier, Klaus Kratochwill, Georg Stary, Ralf Schmidt, Lisa Wagar, Klaus G. Schmetterer
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funder: Austrian Science Fund
OpenAlex ID: W4416449871
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