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The composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in coeliac disease
  1. Frederike Schmitz1,
  2. Yvonne Kooy-Winkelaar1,
  3. Anna-Sophia Wiekmeijer1,
  4. Martijn H Brugman,
  5. M Luisa Mearin1,2,
  6. Chris Mulder3,
  7. Susana Chuva de Sousa Lopes4,
  8. Christine L Mummery4,
  9. Frank JT Staal1,
  10. Jeroen van Bergen1,
  11. Frits Koning1
  1. 1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Gastroenterology, Free University Medical Center, Amsterdam, The Netherlands
  4. 4Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Frits Koning, Department of Immunohematology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands; f.koning{at}lumc.nl

Abstract

Objective Coeliac disease (CD), a gluten-induced enteropathy, alters the composition and function of duodenal intraepithelial T cells. The intestine also harbours four types of CD3-negative intraepithelial lymphocytes (IELs) with largely unknown function: CD56CD127, CD56CD127+, CD56+CD127 and CD56+CD127+. Here we aimed to gain insight into the potential function of these innate IELs in health and disease.

Design We determined the phenotypes, relative abundance and differentiation potential of these innate IEL subsets in duodenal biopsies from controls and patients with CD or patients with refractory CD type II (RCDII).

Results Hierarchical clustering analysis of the expression of 15 natural killer and T cell surface markers showed that innate IELs differed markedly from innate peripheral blood lymphocytes and divided innate IEL subsets into two main branches: a CD127 branch expressing high levels of interleukin (IL) 2/15Rβ but no IL-21R, and a CD127+ branch with the opposite phenotype. While CD was characterised by the contraction of all four innate IEL subsets, a selective expansion of CD56CD127 and CD56CD127+ innate IEL was detected in RCDII. In vitro, in the presence of IL-15, CD56CD127 IEL from controls and patients with CD, but not from patients with RCDII, differentiated into functional natural killer and T cells, the latter largely dependent on notch-signalling. Furthermore, compared with non-coeliac controls, CD56CD127 IEL from patients with CD expressed more intracellular CD3ε and CD3γ and gave more pronounced T cell differentiation.

Conclusions Thus, we demonstrate previously unappreciated diversity and plasticity of the innate IEL compartment and its loss of differentiation potential in patients with RCDII.

  • CELIAC DISEASE
  • CELL BIOLOGY
  • CELLULAR IMMUNOLOGY
  • GUT IMMUNOLOGY

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