Dysregulated monocytes and macrophages in autoimmune disease

Dysregulated monocytes and macrophages are central drivers of chronic inflammation and tissue destruction in autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS) (Navegante et al., 2021, International Journal of Molecular Sciences). These cells exhibit aberrant activation patterns, characterized by the overproduction of pro-inflammatory cytokines like TNF-alpha, IL-6, and IL-1beta, and a failure to transition from a pro-inflammatory M1 phenotype to a pro-resolving M2 phenotype (Udalova et al., 2016, Nature Reviews Rheumatology). In RA, for instance, macrophage-derived cytokines are primary mediators of synovial inflammation and bone erosion (Kinne et al., 2007, Arthritis Research & Therapy). Beyond cytokine production, these cells act as potent antigen-presenting cells that sustain T-cell activation in the target organs. Therapeutic intervention typically involves broad immunosuppression or specific blockade of the signaling pathways (e.g., JAK/STAT) and cytokines that these cells produce (Ma et al., 2019, Frontiers in Immunology). While they are not a single molecular target, their recruitment, activation, and effector functions are the focus of numerous approved and investigational therapies aimed at restoring immune homeostasis.

Other names

Pathogenic myeloid cellsActivated monocytesInflammatory macrophagesMonocyte-derived macrophages (MDMs)M1-polarized macrophages

Therapeutic strategies involve the neutralization of macrophage-derived cytokines (e.g., TNF, IL-6), inhibition of intracellular signaling pathways (e.g., JAK/STAT), or modulation of cell recruitment and polarization (Ma et al., 2019, Frontiers in Immunology).