Antimicrobial peptide LL‐37 promotes antigen‐specific immune responses in mice by enhancing Th17‐skewed mucosal and systemic immunities

The human antimicrobial peptide LL‐37 is known to have chemotactic and modulatory activities on various cells including monocytes, T cells, and epithelial cells. Given that LL‐37 enhances chemotactic attraction and modulates the activity of DCs, it is conceivable that it might play a role as an immune adjuvant by skewing the immune environment toward immunostimulatory conditions. In this study, we characterized the mucosal adjuvant activity of LL‐37 using model and pathogenic Ags. When LL‐37‐conjugated Ag was administered orally to mice, a tolerogenic Peyer's patch environment was altered to cell populations containing IL‐6‐secreting CD11c⁺, CD11c⁺CD70⁺, and Th17 cells capable of evoking a subsequent LL‐37‐conjugated Ag‐specific immune response in both systemic and mucosal immune compartments. In addition, we showed presentation of formyl peptide receptor, an LL‐37 receptor, on M cells, which may aid the initiation of an LL‐37‐mediated enhanced immune response through targeting and transcytosis of the conjugated Ag. Based on our findings, we conclude that LL‐37 has potential as an oral mucosal adjuvant, not only by enhancing the delivery of LL‐37‐conjugated Ag to M cells, but also by triggering T‐cell‐mediated Ag‐specific immune responses through modulation of the mucosal immune environment.