Defensins are cationic antimicrobial peptides that play an important role in innate immunity by primarily acting against microbes. Their antimicrobial properties have been widely studied and are well understood. Defensins contribute to regulation of host immunity also. Their effects on cells of the host however are less well understood. Here, we report on the pro-inflammatory and apoptotic properties of Human Defensin 5, the major antimicrobial peptide of ileal Paneth cells. We find that HD-5 up-regulates expression of genes involved in cell survival and inflammation in a NF-kB-dependent fashion in epithelial cells. Further, we find that HD-5 has pro-apoptotic effects on intestinal epithelial cells as well as primary CD4+ T cells. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.