title: Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Egle
authors.initials: E
authors.lastname: Kvedaraite
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Magda
authors.initials: M
authors.lastname: Lourda
authors.affiliation: Paediatric Gastroenterology, Hepatology and Nutrition Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Maja
authors.initials: M
authors.lastname: Ideström
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Puran
authors.initials: P
authors.lastname: Chen
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Selma
authors.initials: S
authors.lastname: Olsson-Åkefeldt
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Forkel
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Désirée
authors.initials: D
authors.lastname: Gavhed
authors.affiliation: Department of Clinical Science, Gastromedical Center, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lindforss
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Mjösberg
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D053759:Interleukin-23 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D020556:Neutrophil Infiltration / Q000276:immunology*; D062072:Patient Acuity; D018123:Receptors, Interleukin / Q000378:metabolism*
chemical_list: C515500:IL23R protein, human; D053759:Interleukin-23; D016209:Interleukin-8; D018123:Receptors, Interleukin
keywords: GUT IMMUNOLOGY; GUT INFLAMMATION; IBD BASIC RESEARCH; IMAGE ANALYSIS; INFLAMMATORY CELLS