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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
655
Pim Kinases as Therapeutic Targets in Early Rheumatoid Arthritis.
Nicola J Maney1, Henrique Lemos1, Ben Barron-Millar1
1Newcastle University Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Arthritis & Rheumatology (Hoboken, N.J.)
|March 29, 2021
Summary
Proviral integration site for Moloney murine leukemia virus 1 (Pim-1) kinases are elevated in early rheumatoid arthritis (RA). Inhibiting these kinases reduced inflammation and arthritis progression in mouse models, suggesting potential therapeutic use in RA patients.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Proviral integration site for Moloney murine leukemia virus 1 (Pim-1) is an oncoprotein and therapeutic target in cancer.
- Pim-1 is implicated in human autoimmunity.
- This study investigates Pim-1 family members as potential therapeutic targets in early rheumatoid arthritis (RA).
Purpose of the Study:
- To investigate Pim-1 and its family members as potential therapeutic targets in early RA.
- To validate a flow cytometry assay for PIM1 transcript measurement as a biomarker of Pim-1 activity.
- To assess the functional consequences of Pim kinase inhibition in CD4+ T cells and in a mouse model of arthritis.
Main Methods:
- Validated a flow cytometry assay for PIM1 transcript measurement in peripheral blood mononuclear cells.
- Determined synovial protein expression using multiplex immunofluorescence.
- Assessed functional consequences of Pim kinase family manipulation in CD4+ T cells and in mice with collagen-induced arthritis (CIA).
Main Results:
- PIM1 transcript levels were significantly higher in early RA patients compared to other diseases.
- Pim-1 protein levels were up-regulated in synovial CD4+ T cells from early RA patients.
- Pim kinase inhibitors restrained T cell activation, proliferation, and pro-inflammatory cytokine production, while expanding Treg cells. Pim inhibitors limited arthritis progression and cartilage destruction in CIA mice.
Conclusions:
- Pim kinases are plausible therapeutic targets in a subgroup of early RA patients.
- Repurposing of Pim inhibitors for RA should be considered.
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