The roles of cathelicidin LL-37 in immune defences and... : Current Opinion in Hematology (original) (raw)

Myeloid Biology: Edited by David Dale

The roles of cathelicidin LL-37 in immune defences and novel clinical applications

Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, Canada

Correspondence to Robert E.W. Hancock, Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, V6T 1Z4, Canada Tel: +1 604 822 2682; fax: +1 604 827 5566; e-mail: [email protected]

Abstract

Purpose of review

LL-37 is the only member of the cathelicidin family of host defence peptides expressed in humans. It is primarily produced by phagocytic leucocytes and epithelial cells, and mediates a wide range of biological responses: direct killing of microorganisms, chemotaxis and chemokine induction, regulation of inflammatory responses, as well as adjuvant, angiogenic and wound healing effects. In this review we will cover the recent advances in the understanding of LL-37 biology: its activities, the mechanisms of its induction and roles in immune defence.

Recent findings

Recent studies advanced our understanding of the mechanisms controlling LL-37 expression, demonstrating the key involvement of the vitamin D3 and the hypoxia response pathways, and the impacts of commensal and pathogenic microorganisms on its production. The synergistic and antagonistic interactions between LL-37 and other immune mediators have been further elucidated. Furthermore, studies in animal models and human patients further characterized the roles of cathelicidins in immunity, with roles in infectious and inflammatory conditions. The underlying properties of LL-37 have been exploited to create innate defence regulator peptides that represent a novel immunomodulatory approach to treating infections.

Summary

The understanding of the biological properties and functions of LL-37 and other host defence peptides advances our knowledge of innate immunity, the interactions of the host with pathogens and the microflora, as well as the pathology of infectious and inflammatory diseases, creating many strategies and opportunities for therapeutic intervention.