title: Antimicrobial peptide LL-37 promotes antigen-specific immune responses in mice by enhancing Th17-skewed mucosal and systemic immunities.
abstract: 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.
authors: Department of Molecular Biology, Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.|Research Center of Bioactive Materials, Department of Bioactive Material Sciences, Chonbuk National University, Jeonju, Korea.
authors: Sae-Hae
authors: SH
authors: Kim
authors: Department of Molecular Biology, Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.
authors: In-Young
authors: IY
authors: Yang
authors: Jeonju Biomaterials Institute, Chonbuk National University, Jeonju, Korea.
authors: Ju
authors: J
authors: Kim
authors: Department of Oral Microbiology, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
authors: Kyung-Yeol
authors: KY
authors: Lee
authors: Department of Molecular Biology, Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.|Research Center of Bioactive Materials, Department of Bioactive Material Sciences, Chonbuk National University, Jeonju, Korea.
authors: Yong-Suk
authors: YS
authors: Jang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000008:administration & dosage* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D053059:Dengue Vaccines / Q000276:immunology; D005260:Female; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D053059:Dengue Vaccines; D007071:Immunoglobulin A, Secretory; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Antimicrobial peptide; LL-37; Mucosal immunity; Systemic immunity; Th17