Gliadin regulates the NK-dendritic cell cross-talk by HLA-E surface stabilization.
We analyzed the autologous NK cell interaction with gliadin-presenting dendritic cells. Gliadin is the known Ag priming the celiac disease (CD) pathogenesis. We demonstrate that gliadin prevents immature dendritic cells (iDCs) elimination by NK cells. Furthermore, cooperation between human NK cells-iDCs and T cells increases IFN-gamma production of anti-gliadin immune response. Gliadin fractions were analyzed for their capability to stabilize HLA-E molecules. The alpha and omega fractions conferred the protection from NK cell lysis to iDCs and increased their HLA-E expression. Gliadin pancreatic enzyme digest and a peptide derived from gliadin alpha increased HLA-E levels on murine RMA-S/HLA-E-transfected cells. Analysis of HLA-E expression in the small intestinal mucosa of gluten-containing diet celiac patients and organ culture experiments confirmed the in vitro data.
Terrazzano
Giuseppe
G
Department of Cellular and Molecular Biology and Pathology, University Federico II, Naples, Italy. terrazza@unina.it
Sica
Michela
M
Gianfrani
Carmen
C
Mazzarella
Giuseppe
G
Maurano
Francesco
F
De Giulio
Beatrice
B
de Saint-Mezard
Sophie
S
Zanzi
Delia
D
Maiuri
Luigi
L
Londei
Marco
M
Jabri
Bana
B
Troncone
Riccardo
R
Auricchio
Salvatore
S
Zappacosta
Serafino
S
Carbone
Ennio
E
D000293:Adolescent; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002648:Child; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D005903:Gliadin / Q000494:pharmacology*; D006680:HLA Antigens / Q000096:biosynthesis / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007782:Lactoglobulins / Q000502:physiology; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D010455:Peptides / Q000502:physiology; D000097625:HLA-E Antigens
D018984:Epitopes, T-Lymphocyte; D005903:Gliadin; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007782:Lactoglobulins; D010455:Peptides; D000097625:HLA-E Antigens