Figure 2.

Context-dependent effects of type I interferons. In the context of systemic lupus erythematosus (SLE) (left-hand side), type I interferons are probably pathogenic by the following mechanisms: (1) augmenting humoral responses and production of complement-fixing pathogenic antibodies (induce generation of T follicular helper cells (Tfh), stimulate formation of germinal centers and enhance survival of B cells and differentiation to plasmablasts and antibody-producing plasma cells); (2) activating immature dendritic cells (DCs), braking peripheral tolerance to self-antigens; (3) promoting T-helper type 1 (Th1) differentiation; (4) promoting natural killer (NK) cell-mediated and CD8-mediated cytotoxicity; (5) inducing production of chemokines that recruit inflammatory cells at sites of immune complex deposition; and (6) priming myeloid cells for enhanced responses to inflammatory stimuli. In the context of multiple sclerosis (MS), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) (right-hand side), type I interferons are potentially anti-inflammatory and tissue protective by: (1) inhibiting generation of Th17 cells; (2) increasing anti-inflammatory mediators and decreasing proinflammatory mediators; (3) suppressing angiogenesis; (4) reducing tissue invasion of inflammatory cells; (5) shifting the balance of proteases versus protease inhibitors in favor of inhibitors; and (6) suppressing osteoclastogenesis. Ab, antibody; STAT = signal transducer and activator of transcription.