Cathelicidin LL-37 constructs immune-stimulatory microenvironment in mucosal immune system

Intestinal epithelial cells are exposed to microbes and contribute to establish tolerogenic microenvironment for maintaining mucosal homeostasis. In contrast, Peyer’s patch, a mucosal immune inductive site, needs to maintain immunostimulatory microenvironment to induce antigen-specific immune responses, although regulatory mechanism is not clearly defined. We here suggest antimicrobial peptide LL-37 as a mucosal immune-stimulatory molecule. LL-37 is known to have chemotactic and modulatory activity on various cells including monocytes, T cells, and epithelial cells in systemic immune system, but its role in gut mucosal area is unclear. We hypothesized that LL-37 may play a role as an immune modulator by skewing the immune environment toward immune-stimulatory conditions. When LL-37-conjugated antigen was administered orally to mice, we found that cell populations of a tolerogenic Peyer’s patch environment was shifted to those containing IL-6-secreting CD11c⁺ cells, CD11c⁺CD70⁺ cells, and Th17 cells capable of evoking a subsequent antigen-specific immune response in both systemic and mucosal immune compartments. Collectively, we conclude that LL-37 is able to not only act as mucosal stimulator but also be utilized as oral mucosal adjuvant. (S.-H. Kim, Y. N. Kim, H.-Y. Lee, and J. Park were supported by BK21 Plus program in the Department of Bioactive Material Sciences. This study was supported by the Basic Science Research Program, NRF-2014R1A1A3051207 (S.-H. Kim) and NRF-2013R1A2A2A01014459 (Y.-S. Jang).