A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
PIM kinases regulate early human Th17 cell differentiation
Tekijät: Buchacher Tanja, Shetty Ankitha, Koskela Saara A., Smolander Johannes, Kaukonen Riina, Sousa Antonio G. G., Junttila Sini, Laiho Asta, Rundquist Olof, Lonnberg Tapio, Marson Alexander, Rasool Omid, L. Laura, Lahesmaa Riitta
Kustantaja: Elsevier
Julkaisuvuosi: 2023
Journal: Cell Reports
Tietokannassa oleva lehden nimi: CELL REPORTS
Lehden akronyymi: CELL REP
Artikkelin numero: 113469
Vuosikerta: 42
Numero: 12
ISSN: 2211-1247
eISSN: 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2023.113469
Verkko-osoite: https://doi.org/10.1016/j.celrep.2023.113469
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/182292420
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
