摘要: Antiinflammatory therapeutics are commonly used to combat a vast array of chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and Crohn’s disease (1). These chronic inflammatory diseases affect ∼5 to 7% of the population, creating a significant socioeconomic burden and impact on patients’ quality of life (2). Current therapies have revolved around the use of anti-tumor necrosis factor (TNF) antibodies, aiming to block the activity of TNF-α and cytokines such as interleukin (IL)-1, IL-6, and granulocyte-macrophage colony-stimulating factor that make up its downstream proinflammatory cascade (3). Although these anti-TNF therapeutics have shown efficacy over the past two decades, there are several drawbacks to this approach, including the need for repeated injections, patient compliance issues, tolerability, and the development of antidrug antibodies, which could lead to reduction of drug efficacy and adverse side effects such as increased risk of infections and hypersensitivity (4, 5). In PNAS, Hainline et al. (6) developed an alternative active immunotherapy approach that incorporates an engineered fragment of complement protein C3dg and peptide epitopes derived from the soluble form of TNF into a self-assembled supramolecular nanofiber. Administration of these nanofibers as an immunomodulatory vaccine successfully lowered inflammatory signatures in models of TNF-driven septic shock and psoriasis. Despite the simplicity of the components, these nanofibers are shown by the authors to act in multiple complementary ways to modulate the immune system (Fig. 1). First, C3dg acts as a molecular adjuvant to promote B cell activation and costimulation of the complement receptor 2 (CD21) (7), helping to break tolerance against TNF and raise endogenous antibodies against the cytokine. Second, antibodies are directly raised against C3dg, with the potential to limit complement effector functions. Finally, autoreactive helper T cells specific for peptides derived from C3dg … [↵][1]1To whom correspondence may be addressed. Email: djirvine{at}mit.edu. [1]: #xref-corresp-1-1