Rheumatoid arthritis associated cytokines and therapeutics modulate immune checkpoint receptor expression on T cells

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation.
• Cytokines play a critical role in RA pathogenesis.
• Immune checkpoint receptors (IRs) on T cells regulate immune responses and are implicated in autoimmune diseases.

Purpose of the Study:

• To investigate the impact of RA-associated cytokines and standard of care (SOC) therapeutics on immune checkpoint receptor (IR) expression on T cells.
• To gain insights into RA disease pathology and identify potential therapeutic avenues.

Main Methods:

• Assessed IR expression on T cells using flow cytometry.
• Cultured T cells with exogenous cytokines or RA patient synovial fluid.
• Evaluated the effects of cytokine neutralizing antibodies and SOC therapeutics (glucocorticoids, TNF, IL-6 receptor, and JAK inhibitors).
• Measured cytokine secretion profiles.

Main Results:

• RA-associated cytokines modulated IR expression on T cells.
• Distinct regulation of IR expression observed with IL-10, IFNα/β, and TNF.
• Key cytokines (IL-6, IL-10, IL-12, IFNs, TNF) drove increased expression of TIM-3, PD-1, LAG-3, and CD28 in response to RA synovial fluid.
• SOC RA therapeutics modulated IR and cytokine expression.

Conclusions:

• There is an intricate relationship between cytokines and IRs in autoimmune pathology.
• Modulation of IR expression by RA cytokines and SOC therapeutics offers new insights for targeted RA treatments.