Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease

Author:

Fiz‐López Aida1ORCID,De Prado Ángel12,Arribas‐Rodríguez Elisa1,García‐Alonso Francisco Javier2,Izquierdo Sandra3,Martín‐Muñoz Álvaro4,Garrote José A.1ORCID,Arranz Eduardo1,Barrio Jesús2,Fernández‐Salazar Luis35,Bernardo David16

Affiliation:

1. Mucosal Immunology Lab Unidad de Excelencia Instituto Biomedicina y Genética Molecular (IBGM), Universidad de Valladolid‐CSIC Valladolid Spain

2. Servicio de Gastroenterología Hospital Universitario Río Hortega Valladolid Spain

3. Servicio de Gastroenterología Hospital Clínico Universitario Valladolid Spain

4. Cytometry Facility Unidad de Excelencia Instituto Biomedicina y Genética Molecular (IBGM, Universidad de Valladolid‐CSIC) Valladolid Spain

5. Departamento de Medicina, Dermatología y Toxicología Universidad de Valladolid Valladolid Spain

6. Centro de Investigaciones Biomédicas en Red de Enfermedades Infecciosas (CIBERINFEC) Madrid Spain

Abstract

AbstractBackgroundIntraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum.MethodsIntraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry.ResultsOur results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin‐15 (IL‐15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL‐15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL‐15 receptor was not increased either on Intraepithelial lymphocytes from CD patients.ConclusionsIL‐15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.

Funder

Ministerio de Ciencia e Innovación

Junta de Castilla y León

Publisher

Wiley

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