title: Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts.
abstract: We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells, while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3(-) IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3(-) IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3(-) CD127(+) cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3(-) IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ(+) IL-22(+) population was observed. Epithelial cell-depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3(-) IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56(+) , NKp44(+) , CCR6(+) , CD127(-) , cytotoxicity, and IFNγ secretion), ILC3 (CD56(+) , NKp44(+) , IL-23R(+) , CCR6(+) , RORγt(+) , and IL-22 secretion), and intermediate ILC1-ILC3 phenotypes (IFNγ(+) IL-22(+) ). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.
authors: Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.
authors: P
authors: P
authors: Talayero
authors: Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.
authors: E
authors: E
authors: Mancebo
authors: Department of General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain.
authors: J
authors: J
authors: Calvo-Pulido
authors: Department of Gastroenterology, University Hospital 12 de Octubre, Madrid, Spain.
authors: S
authors: S
authors: Rodríguez-Muñoz
authors: Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.
authors: I
authors: I
authors: Bernardo
authors: Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.
authors: R
authors: R
authors: Laguna-Goya
authors: I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.
authors: F L
authors: FL
authors: Cano-Romero
authors: Department of General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain.
authors: A
authors: A
authors: García-Sesma
authors: Department of General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain.
authors: C
authors: C
authors: Loinaz
authors: I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.|Department of General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain.|School of Medicine, Complutense University, Madrid, Spain.
authors: C
authors: C
authors: Jiménez
authors: Department of General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain.
authors: I
authors: I
authors: Justo
authors: Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.|School of Medicine, Complutense University, Madrid, Spain.|Section of Immunology, San Pablo CEU University, Madrid, Spain.
authors: E
authors: E
authors: Paz-Artal
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D015703:Antigens, CD / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D007410:Intestinal Diseases / Q000276:immunology / Q000601:surgery*; D007422:Intestines / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; D039001:Integrin alpha Chains; C091367:alpha E integrins
keywords: basic (laboratory) research / science; immunobiology; innate immunity; intestinal (allograft) function / dysfunction; intestine / multivisceral transplantation; lymphocyte biology; mucosal immunity; natural killer (NK) cells / NK receptors; translational research / science