Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps.

Zysset, Daniel; Montani, Matteo; Spalinger, Johannes; Schibli, Susanne; Zlobec, Inti; Mueller, Christoph; Sokollik, Christiane (2021). Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps. Clinical and translational gastroenterology, 12(6), e00361. Wolters Kluwer Health 10.14309/ctg.0000000000000361

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INTRODUCTION

Solitary juvenile polyps (JP) are characterized by a benign disease course with low recurrence rate but present with signs of intestinal inflammation. To better understand the underlying pathogenesis, we performed histological and molecular evaluation targeting distinct immune mechanisms.

METHODS

Pediatric patients with JP (n = 12), with treatment-naïve inflammatory bowel disease (IBD; [n = 41]) as inflammatory control, and non-IBD controls (n = 14) were investigated. For a comparative analysis of infiltrating immune cells, a next-generation tissue microarray of biopsies was assembled, immunostained, and scored. Targeted transcriptional profiling was performed using a customized immunology panel.

RESULTS

In JP, a predominant accumulation of neutrophils and eosinophils was observed. RNA expression profiles revealed increased levels of CXCL8, CXCL5, and CCL11 transcripts in JP, indicating an enhanced recruitment of neutrophils and eosinophils. Moreover, messenger RNA levels of the proinflammatory cytokine IL1b and the inflammation-amplifying receptor TREM1 were higher in JP, whereas we could not find signs of a functionally polarized Tcell response in JP when compared with IBD.

DISCUSSION

Patients with JP and patients with treatment-naïve IBD have distinct cell infiltrates during active disease. The ample presence of eosinophils in JP supports neutrophil accumulation, which is responsible for the elevated release of calprotectin. Intriguingly, however, we were not able to identify a functionally polarized T-cell response in JP, which indicates that during the acute onset of inflammation in JP, a potent adaptive immune memory is not established. This may explain the low reoccurrence rate of JP.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Zysset, Daniel; Montani, Matteo; Schibli, Susanne; Zlobec, Inti; Müller, Christoph and Sokollik, Christiane

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

2155-384X

Publisher:

Wolters Kluwer Health

Language:

English

Submitter:

Christa Hagert

Date Deposited:

22 Jun 2021 14:47

Last Modified:

27 Jun 2021 03:08

Publisher DOI:

10.14309/ctg.0000000000000361

PubMed ID:

34060497

BORIS DOI:

10.48350/156964

URI:

https://boris.unibe.ch/id/eprint/156964

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