Autocrine IL-15 mediates intestinal epithelial cell death via the activation of neighboring intraepithelial NK cells.
Intestinal intraepithelial lymphocytes (IELs), which reside between the basolateral faces of intestinal epithelial cells (IECs), provide a first-line defense against pathogens via their cytotoxic activity. Although IEC-derived IL-7 and IL-15 are key regulatory cytokines for the development and activation of IELs, we report here that IL-15 but not IL-7 mediates the reciprocal interaction between IELs and IECs, an important interaction for the regulation of appropriate mucosal immunohomeostasis. IL-15-treated IELs induced cell death in IECs via the cytotoxic activity in vitro. Among the different subsets of IL-15-treated IELs, CD4(-)CD8(-)TCR(-) IELs, which express NK marker (DX5 or NK1.1), showed the most potent syngenic IEC killing activity. These intraepithelial NK cells expressed Ly-49 molecules, NKG2 receptors, and perforin. These results suggest the possibility that the cell death program of IECs could be regulated by self-produced IL-15 through the activation of intraepithelial NK cells.
Kinoshita
Naotoshi
N
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Hiroi
Takachika
T
Ohta
Noriyuki
N
Fukuyama
Satoshi
S
Park
Eun Jeong
EJ
Kiyono
Hiroshi
H
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D066298:In Vitro Techniques; D019409:Interleukin-15 / Q000378:metabolism* / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D019409:Interleukin-15; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D054353:Perforin