RT Journal Article
SR Electronic
T1 Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1632
OP 1641
DO 10.1136/gutjnl-2014-309014
VO 65
IS 10
A1 Egle Kvedaraite
A1 Magda Lourda
A1 Maja Ideström
A1 Puran Chen
A1 Selma Olsson-Åkefeldt
A1 Marianne Forkel
A1 Désirée Gavhed
A1 Ulrik Lindforss
A1 Jenny Mjösberg
A1 Jan-Inge Henter
A1 Mattias Svensson
YR 2016
UL http://gut.bmj.com/content/65/10/1632.abstract
AB 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.