Celiac Disease-Related Inflammation Is Marked by Reduction of Nkp44/Nkp46-Double Positive Natural Killer Cells

• Published in: PloS one 2016-05, Vol.11 (5), p.e0155103
• Main Authors: Marafini, Irene, Monteleone, Ivan, Di Fusco, Davide, Sedda, Silvia, Cupi, Maria Laura, Fina, Daniele, Paoluzi, Alessandro Omero, Pallone, Francesco, Monteleone, Giovanni
• Format: Article
• Language: English
• Subjects: Active control; Autoimmune diseases; Bacteria - metabolism; Biology and life sciences; Biopsy; Care and treatment; Celiac disease; Celiac Disease - complications; Celiac Disease - immunology; Celiac Disease - microbiology; Celiac Disease - pathology; Cell Count; Complications and side effects; Cytokines; Cytomegalovirus; Cytometry; Cytotoxicity; Down-regulation; Epithelial Cells - metabolism; Escape systems; Gastroenterology; Gluten; Granzyme B; Granzymes - metabolism; Humans; Immune system; Immunology; Infections; Inflammation; Inflammation - complications; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Influence; Interleukin 22; Interleukins - metabolism; Intestinal bypass; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Killer cells; Killer Cells, Natural - immunology; Leukocytes (mononuclear); Ligands; Lymphocytes B; Lymphocytes T; Medicine; Medicine and health sciences; Natural Cytotoxicity Triggering Receptor 1 - metabolism; Natural Cytotoxicity Triggering Receptor 2 - metabolism; Natural Cytotoxicity Triggering Receptor 3 - metabolism; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily K - metabolism; NKG2 antigen; Pathogens; Patients; Proteins; Receptors; Research and Analysis Methods; Risk factors; Small intestine; T cell receptors; Toll-like receptors; Toll-Like Receptors - metabolism; Tumor necrosis factor-α; Viral infections; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0155103

Natural killer (NK) cells are a first line of defence against viruses and down-regulation of NK cell cytotoxic receptors represents one of the strategies by which viruses escape the host's immune system. Since onset of celiac disease (CD), a gluten-driven enteropathy, has been associated with viral infections, we examined whether CD-associated inflammation is characterized by abnormal distribution of NK cell receptors involved in recognition of viral-infected cells. Intraepithelial mononuclear cells, isolated from duodenal biopsies of active and inactive CD patients and healthy controls (CTR) and jejunal specimens of obese subjects undergoing gastro-intestinal bypass, were analysed for NK cell markers by flow-cytometry. Expression of granzyme B, interleukin (IL)-22 and tumor necrosis factor (TNF)-α was as assessed in freshly isolated and toll-like receptor (TLR) ligand-stimulated cells. The percentages of total NK cells and NKT cells did not significantly differ between CD patients and CTR. In active CD, the fractions of NKp30+ NK cells, NKG2D+ NK cells and NKG2D+ NKT cells were significantly increased as compared to inactive CD patients and CTR. In contrast, CD-associated inflammation was marked by diminished presence of NKG2A+ NK cells and NKG2A+ NKT cells. The fractions of NK cells and NKT cells expressing either NKp44 or NKp46 did not differ between CD and controls, but in CD less NK cells and NKT cells co-expressed these receptors. NKp44/NKp46-double positive cells produced granzyme B and IL-22 but not TNF-α and responded to TLR ligands with enhanced expression of granzyme B. These data indicate that active phase of CD associates with reduced presence of NKp44/NKp46-double positive NK cells and NKT cells in the epithelial compartment.