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Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD
  1. Egle Kvedaraite1,2,
  2. Magda Lourda1,2,
  3. Maja Ideström3,
  4. Puran Chen1,
  5. Selma Olsson-Åkefeldt2,
  6. Marianne Forkel1,
  7. Désirée Gavhed2,
  8. Ulrik Lindforss4,
  9. Jenny Mjösberg1,
  10. Jan-Inge Henter2,
  11. Mattias Svensson1
  1. 1Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
  2. 2Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
  3. 3Paediatric Gastroenterology, Hepatology and Nutrition Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  4. 4Department of Clinical Science, Gastromedical Center, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
  1. Correspondence to Dr Mattias Svensson, Department of Medicine, Center for Infectious Medicine, F59, Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden; mattias.svensson{at}ki.se

Abstract

Objective In IBD, interleukin-23 (IL-23) and its receptor (IL-23R) are implicated in disease initiation and progression. Novel insight into which cells produce IL-23 at the site of inflammation at an early stage of IBD will promote the development of new tools for diagnosis, treatment and patient monitoring. We examined the cellular source of IL-23 in colon tissue of untreated newly diagnosed paediatric patients with IBD.

Design Colon tissues from IBD and non-IBD patients were analysed by quantitative real-time PCR (qPCR), immunofluorescence confocal microscopy and flow cytometry after appropriate sample preparation. Blood samples from IBD and non-IBD patients and healthy controls were analysed using flow cytometry and qPCR.

Results We discovered that tissue-infiltrating neutrophils were the main source of IL-23 in the colon of paediatric patients with IBD, while IL-23+ human leucocyte antigen-DR+ or IL-23+CD14+ cells were scarce or non-detectable, respectively. The colonic IL-23+ neutrophils expressed C-X-C motif (CXC)R1 and CXCR2, receptors for the CXC ligand 8 (CXCL8) chemokine family, and a corresponding CXCR1+CXCR2+IL-23+subpopulation of neutrophils was also identified in the blood of both patients with IBD and healthy individuals. However, CXCL8-family chemokines were only elevated in colon tissue from patients with IBD.

Conclusions This study provides the first evidence of CXCR1+CXCR2+IL-23-producing neutrophils that infiltrate and accumulate in inflamed colon tissue of patients with IBD. Thus, this novel source of IL-23 may play a key role in disease progression and will be important to take into consideration in the development of future strategies to monitor, treat and prevent IBD.

  • GUT INFLAMMATION
  • GUT IMMUNOLOGY
  • IBD BASIC RESEARCH
  • IMAGE ANALYSIS
  • INFLAMMATORY CELLS

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