1. Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD
- Author
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Puran Chen, Jan-Inge Henter, Jenny Mjösberg, Egle Kvedaraite, Maja Ideström, Magda Lourda, Selma Olsson-Åkefeldt, Marianne Forkel, Mattias Svensson, Désirée Gavhed, and Ulrik Lindforss
- Subjects
Male ,Chemokine ,Adolescent ,Colon ,CD14 ,Inflammation ,Immunofluorescence ,Interleukin-23 ,Flow cytometry ,medicine ,Interleukin 23 ,Humans ,Interleukin 8 ,CXC chemokine receptors ,Child ,medicine.diagnostic_test ,biology ,business.industry ,Interleukin-8 ,Patient Acuity ,Gastroenterology ,Receptors, Interleukin ,Inflammatory Bowel Diseases ,digestive system diseases ,Neutrophil Infiltration ,Child, Preschool ,Immunology ,Disease Progression ,biology.protein ,Female ,medicine.symptom ,business - 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.
- Published
- 2015
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