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Lymphocyte modulation by tofacitinib in patients with rheumatoid arthritis

Natasa Isailovic1, Angela Ceribelli1,2, Gilberto Cincinelli1

  • 1Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy.

Clinical and Experimental Immunology
|April 26, 2021
PubMed

Insights

Tofacitinib rapidly impacts rheumatoid arthritis (RA) B cells responding to collagen epitopes. This JAK inhibitor modulates inflammatory cytokines and partially prevents altered IL-10 responses in RA patients.

Area of Science:

  • Immunology
  • Rheumatology
  • Pharmacology

Background:

  • Rheumatoid arthritis (RA) involves aberrant immune responses to self-antigens, including collagen.
  • Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways are crucial in RA pathogenesis.
  • Tofacitinib is an oral JAK inhibitor approved for active RA treatment.

Purpose of the Study:

  • To investigate the effects of tofacitinib on lymphocyte responses to collagen epitopes in RA patients.
  • To analyze tofacitinib's impact on cytokine production by B and T cells stimulated with collagen peptides.
  • To assess tofacitinib's influence on interleukin-10 (IL-10) modulation in RA B cells.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls were cultured with collagen peptides or mitogens.
  • Cells were treated with 100 nM tofacitinib and analyzed by fluorescence-activated cell sorting (FACS).
  • Cytokine levels in supernatants were measured using enzyme-linked immunosorbent assay (ELISA).

Main Results:

  • Tofacitinib down-regulated inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-17) from stimulated B and T cells in the short term.
  • Significant reductions in IL-17 and IL-6 were observed in PBMC supernatants.
  • Tofacitinib partially prevented the down-modulation of IL-10 in collagen-stimulated RA B cells, unlike in controls.

Conclusions:

  • Tofacitinib exerts a rapid regulatory effect on B cells from RA patients upon stimulation with collagen epitopes.
  • The drug modulates inflammatory cytokine production by lymphocytes.
  • Tofacitinib influences the altered IL-10 response to collagen self-epitopes observed in RA.
Keywords:
Janus kinaseacquired immunitycollagen epitopepost-translational modificationsregulatory effecttargeted synthetic DMARDs

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