Innate Lymphoid cells groups 1 and 3 in the epitelial compartment of functional human intestinal allografts

Talayero, Paloma; Mancebo Sierra, María Esther; Calvo Pulido, Jorge; Rodríguez Muñoz, Sarbelio; Bernardo, I.; Laguna Goya, Rocio; Cano Romero, Francisco; García-Sesma Pérez-Fuentes, Álvaro; Loinaz Segurola, Carmelo; Jiménez Romero, Luis Carlos; Justo Alonso, Iago; Paz Artal, Estela Natividad

Innate Lymphoid cells groups 1 and 3 in the epitelial compartment of functional human intestinal allografts

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https://www.sciencedirect.com/science/article/pii/S1600613522005147?via%3Dihub

Publication date

2016

Publisher

Elsevier

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URI

https://hdl.handle.net/20.500.14352/98794

Citation

Talayero P, Mancebo E, Calvo-Pulido J, Rodríguez-Muñoz S, Bernardo I, Laguna-Goya R, Cano-Romero FL, García-Sesma A, Loinaz C, Jiménez C, Justo I, Paz-Artal E. Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts. Am J Transplant. 2016 Jan;16(1):72-82. doi: 10.1111/ajt.13435

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.